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Gene Information

Gene symbol: CXCR4

Gene name: chemokine (C-X-C motif) receptor 4

HGNC ID: 2561

Synonyms: LESTR, NPY3R, HM89, NPYY3R, D2S201E, fusin, HSY3RR, NPYR, CD184

Related Genes

# Gene Symbol Number of hits
1 AKT1 1 hits
2 BCL6 1 hits
3 CCL19 1 hits
4 CCL2 1 hits
5 CCL21 1 hits
6 CCL28 1 hits
7 CCL4 1 hits
8 CCL5 1 hits
9 CCR1 1 hits
10 CCR10 1 hits
11 CCR2 1 hits
12 CCR3 1 hits
13 CCR4 1 hits
14 CCR5 1 hits
15 CCR6 1 hits
16 CCR7 1 hits
17 CCR9 1 hits
18 CD14 1 hits
19 CD1A 1 hits
20 CD34 1 hits
21 CD4 1 hits
22 CD40 1 hits
23 CD40LG 1 hits
24 CD58 1 hits
25 CD69 1 hits
26 CD79A 1 hits
27 CD80 1 hits
28 CD83 1 hits
29 CD86 1 hits
30 CD8A 1 hits
31 CRP 1 hits
32 CX3CR1 1 hits
33 CXCL10 1 hits
34 CXCL12 1 hits
35 CXCL2 1 hits
36 CXCR3 1 hits
37 CXCR5 1 hits
38 CXCR7 1 hits
39 DOCK2 1 hits
40 ELMO1 1 hits
41 ERVWE1 1 hits
42 FAS 1 hits
43 FASLG 1 hits
44 FCGR3A 1 hits
45 HLA-A 1 hits
46 HSPA14 1 hits
47 HSPA1A 1 hits
48 ICOS 1 hits
49 IFNA1 1 hits
50 IFNB1 1 hits
51 IFNG 1 hits
52 IGF1 1 hits
53 IL10 1 hits
54 IL12A 1 hits
55 IL16 1 hits
56 IL17C 1 hits
57 IL6 1 hits
58 IL8 1 hits
59 ITGAL 1 hits
60 ITGB2 1 hits
61 ITGB7 1 hits
62 IV 1 hits
63 KDR 1 hits
64 KLRB1 1 hits
65 MAF 1 hits
66 MAPK1 1 hits
67 MBL2 1 hits
68 NCAM1 1 hits
69 PDCD1 1 hits
70 PRDM1 1 hits
71 PROM1 1 hits
72 PTPRC 1 hits
73 PYCARD 1 hits
74 SELL 1 hits
75 SPP1 1 hits
76 TEK 1 hits
77 TNFRSF4 1 hits
78 VEGFA 1 hits
79 VHLL 1 hits

Related Sentences

# PMID Sentence
1 9048206 The discovery of distinct chemokine receptors that support entry of T-cell tropic (CXCR-4) and macrophage tropic HIV-1 strains (CCR-5) explains the differences in cell tropism between viral strains, the inability of HIV-1 to infect most nonprimate cells, and the resistance of a small percentage of the population to HIV-1 infection.
2 9658070 CD8(+) T lymphocytes from immunized animals were able to potently suppress SIV replication in autologous SIV-infected CD4(+) T cells.
3 9658070 Suppression of SIV replication by unstimulated CD8(+) T cells required direct contact and was major histocompatibility complex (MHC) restricted.
4 9658070 However, CD3-stimulated CD8(+) T cells produced soluble factors that inhibited SIV replication in an MHC-unrestricted fashion as much as 30-fold.
5 9658070 Supernatants from stimulated CD8(+) T cells were also able to inhibit replication of both CCR5- and CXCR4-dependent human immunodeficiency virus type 1 (HIV-1) strains.
6 9658070 Production of RANTES, macrophage inhibitory protein 1alpha (MIP-1alpha), or MIP-1beta from stimulated CD8(+) T cells of vaccinated animals was almost 10-fold higher than that from stimulated CD8(+) T cells of control animals.
7 9658070 Our results indicate that inhibition of SIV replication by CD8(+) T cells from animals immunized with live attenuated SIV strains involves both MHC-restricted and -unrestricted mechanisms and that MHC-unrestricted inhibition of SIV replication is due principally to soluble factors other than RANTES, MIP-1alpha, and MIP-1beta.
8 9711781 Maturation of human neonatal CD4+ and CD8+ T lymphocytes into Th1/Th2 effectors.
9 9711781 The activation and maturation of neonatal CD4+ T cells is particularly dependent upon the strength of CD28-mediated cosignal which dictates not only the cytokine profile released upon primary activation but also the response to IL-12.
10 9711781 Activation of adult as well as neonatal CD4+ T cells in the context of low CD28 costimulation yields to the production of low levels of only one cytokine, i.e.
11 9711781 In contrast, strong CD28 costimulation supports the production of high levels of type 1 (IL-2, IFN gamma and TNF beta) and low levels of type 2 (IL-4 and IL-13) cytokines by neonatal T cells.
12 9711781 The low levels of naive T cell-derived IL-4 are sufficient to support their development into high IL-4/IL-5 producers by an autocrine pathway.
13 9711781 The ability of IL-12 to prime neonatal CD4+ T cells for increased production of IL-4 (in addition to IFN gamma) is observed only when CD28 cosignal is minimal.
14 9711781 Unlike CD4+ T cells, neonatal CD8+ T cells strictly require exogenous IL-4 to develop into IL-4/IL-5 producers.
15 9711781 Most importantly, anti-CD3/B7-activated neonatal CD8 T cells coexpress CD4 as well as CCR5 and CXCR4 and are susceptible to HIV-1 infection in vitro.
16 9882391 We have characterized sera from healthy volunteers immunized with a monomeric recombinant gp120 (rgp120) derived from a CCR5/CXCR4 (R5X4)-using subtype B isolate of human immunodeficiency virus type (HIV-1), HIV-1W61D, in comparison to sera from long-term HIV-1-infected individuals, using homologous reagents.
17 9882391 Sera from vaccinees and HIV-1 positive subjects had similar binding titers to native monomeric rgp120W61D and showed a similar titer of antibodies inhibiting the binding of soluble CD4 (sCD4) to rgp120W61D.
18 10217580 The effect of immunization on chemokines and CCR5 and CXCR4 coreceptor functions in SIV binding and chemotaxis.
19 10217580 The replication of simian immunodeficiency virus (SIV) in acutely infected CD4+ cells can be inhibited in vitro by CD8-suppressor factors (SF) and beta-chemokines induced by immunization of macaques with SIV gp120 and p27 in Alum.
20 10217580 A comparison between intradermal, naso-rectal-i.m. and targeted iliac lymph node (TILN) routes showed that immunization by the TILN route elicited the most significant increase in CD8-SF and the beta-chemokines RANTES, MIP-1alpha and MIP-1beta.
21 10217580 Furthermore, CD8-SF and the concentrations of RANTES, MIP-1alpha and MIP-1beta increased with secondary immunizations, suggesting that memory CD8+ cells are involved.
22 10217580 Treatment of CD8+ cell culture supernatant with antibodies to RANTES, MIP-1alpha and MIP-1beta neutralized the CD8-SF activity, indicating that blocking the CCR5 by these ligands played an important part in the CD8-SF activity elicited by TILN immunization.
23 10221916 Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs.
24 10470076 Within 1 month of allo-immunization, there was significant upregulation in the concentrations of CD8 cell-derived suppressor factor activity, RANTES, and macrophage inflammatory proteins 1alpha and 1beta.
25 10470076 Allo-immunization also downregulated the proportion of cells with CCR5 and CXCR4 receptors.
26 10486153 They expressed a set of DC-associated markers, such as MHC class II, CD1a, CD4, CD11a, CD40, CD58, CD80, CD83, CD86, and CXCR4.
27 10559349 Although infection by human immunodeficiency virus (HIV) typically requires an interaction between the viral envelope glycoprotein (Env), CD4, and a chemokine receptor, CD4-independent isolates of HIV and simian immunodeficiency virus have been described.
28 10559349 We have derived a variant of HIV-1/IIIB, termed IIIBx, that acquired the ability to utilize CXCR4 without CD4.
29 10559349 This virus infected CD4-negative T and B cells and fused with murine 3T3 cells that expressed human CXCR4 alone.
30 10559349 Remarkably, when the V3 loop of a CCR5-tropic Env was substituted for the IIIBx Env, the resulting chimera was found to utilize CCR5 but remained CD4 independent.
31 10559349 Although infection by human immunodeficiency virus (HIV) typically requires an interaction between the viral envelope glycoprotein (Env), CD4, and a chemokine receptor, CD4-independent isolates of HIV and simian immunodeficiency virus have been described.
32 10559349 We have derived a variant of HIV-1/IIIB, termed IIIBx, that acquired the ability to utilize CXCR4 without CD4.
33 10559349 This virus infected CD4-negative T and B cells and fused with murine 3T3 cells that expressed human CXCR4 alone.
34 10559349 Remarkably, when the V3 loop of a CCR5-tropic Env was substituted for the IIIBx Env, the resulting chimera was found to utilize CCR5 but remained CD4 independent.
35 10603312 Antibodies to the bivalent vaccine formulation neutralized viruses possessing diverse phenotypes, including syncytia-inducing and non-syncytia-inducing primary isolates, viruses using either the CCR5 or the CXCR4 chemokine receptors, and viruses differing in their sensitivity to soluble CD4.
36 10631078 Previous studies demonstrated that the L. chagasi antigen LCR1 stimulates IFN-gamma production from T cells of infected BALB/c mice, and immunization with recombinant LCR1 partially protects against L. chagasi infection.
37 10631078 Splenocytes from mice immunized s.c. with either BCG-LCR1 or BCG-pMV261 and then infected with L. chagasi promastigotes had increased antigen-induced IFN-gamma and reduced IL-10 production compared to splenocytes of control mice.
38 10725402 Immune animals had significantly attenuated disease with lowered viral RNA, interferon-alpha, and chemokine receptor expression (CXCR4 and CCR5) on CD4(+) T cells; these features of infection have been linked to in vitro effects of Tat and respond similarly to extracellular Tat protein produced during infection.
39 10774806 CXCR4 and CCR5 expression on CD4+ T cells in vivo and HIV-1 antigen beta-chemokine production in vitro after treatment with HIV-1 immunogen (REMUNE).
40 10775586 This study demonstrates that (i) supernatants from peripheral blood mononuclear cells (PBMC) stimulated with influenza A virus inhibit replication of CCR5- and CXCR4-tropic HIV-1 isolates prior to reverse transcription; (ii) the HIV-suppressive supernatants can be generated by CD4- or CD8-depleted PBMC; (iii) this anti-HIV activity is partially due to alpha interferon (IFN-alpha), but not to IFN-gamma, IFN-beta, the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES, or interleukin-16; (iv) the anti-HIV activity is generated equally well by PBMC cultured with either infectious or UV-inactivated influenza A virus; and (v) the antiviral activity can be generated by influenza A-stimulated PBMC from HIV-infected individuals.
41 10775586 These findings represent a novel mechanism for inhibition of HIV-1 replication that differs from the previously described CD8 anti-HIV factors (MIP-1alpha, MIP-1beta, RANTES, and CD8 antiviral factor).
42 10841574 While exploring the biological mechanisms behind this natural protection, we found that a significant proportion of peripheral blood mononuclear cells obtained from HIV-2-infected subjects resisted in vitro challenge with CCR5-dependent HIV-1 viruses but not CXCR4-dependent viruses.
43 10942783 Several mutant genes in HIV co-receptors (e.g., CCR5, CCR2 and CXCR4) have been correlated with susceptibility to HIV or/and rate of progression to AIDS.
44 11044111 The analysis revealed that there are fewer immunotypes than genotypes of HIV and that clustering of the isolates did not correlate with either genotypes, coreceptor usage (CCR5 and CXCR4), or geographic origin of the isolates.
45 11333875 We also tested this clone for its ability to use the chemokine receptors CCR1, CCR2b, CCR3, CXCR4, and CCR5 and found that the clone utilizes only CCR5 as the coreceptor for cell entry.
46 11478800 Evidence as a HIV-1 self-defense vaccine of cyclic chimeric dodecapeptide warped from undecapeptidyl arch of extracellular loop 2 in both CCR5 and CXCR4.
47 11478800 Novel conformation-specific antibodies were raised against a cyclic chimeric dodecapeptidyl multiple antigen peptide (cCD-MAP) constructed with a spacer-armed Gly-Asp dipeptide and two pentapeptides (S(169)-Q(170)-K(171)-E(172)-G(173) of CCR5 and E(179)-A(180)-D(181)-D(182)-R(183) of CXCR4) which are components of the undecapeptidyl arch (UPA: from R(168) to C(178) in CCR5, from N(176) to C(186) in CXCR4) of extracellular loop 2 (ECL2) in chemokine receptors (CCR5 and CXCR4).
48 11478800 The antibody reacted with the cells separately expressing CCR5 or CXCR4, but not with those not expressing the coreceptors.
49 11478800 Moreover, the antibody markedly suppressed infection by X4, R5, or R5X4 virus in a dose-dependent manner in a new phenotypic assay for drug susceptibility of HIV-1 using CCR5-expressing Hela/CD4(+) cell clone 1-10 (MAGIC-5).
50 11478800 Evidence as a HIV-1 self-defense vaccine of cyclic chimeric dodecapeptide warped from undecapeptidyl arch of extracellular loop 2 in both CCR5 and CXCR4.
51 11478800 Novel conformation-specific antibodies were raised against a cyclic chimeric dodecapeptidyl multiple antigen peptide (cCD-MAP) constructed with a spacer-armed Gly-Asp dipeptide and two pentapeptides (S(169)-Q(170)-K(171)-E(172)-G(173) of CCR5 and E(179)-A(180)-D(181)-D(182)-R(183) of CXCR4) which are components of the undecapeptidyl arch (UPA: from R(168) to C(178) in CCR5, from N(176) to C(186) in CXCR4) of extracellular loop 2 (ECL2) in chemokine receptors (CCR5 and CXCR4).
52 11478800 The antibody reacted with the cells separately expressing CCR5 or CXCR4, but not with those not expressing the coreceptors.
53 11478800 Moreover, the antibody markedly suppressed infection by X4, R5, or R5X4 virus in a dose-dependent manner in a new phenotypic assay for drug susceptibility of HIV-1 using CCR5-expressing Hela/CD4(+) cell clone 1-10 (MAGIC-5).
54 11478800 Evidence as a HIV-1 self-defense vaccine of cyclic chimeric dodecapeptide warped from undecapeptidyl arch of extracellular loop 2 in both CCR5 and CXCR4.
55 11478800 Novel conformation-specific antibodies were raised against a cyclic chimeric dodecapeptidyl multiple antigen peptide (cCD-MAP) constructed with a spacer-armed Gly-Asp dipeptide and two pentapeptides (S(169)-Q(170)-K(171)-E(172)-G(173) of CCR5 and E(179)-A(180)-D(181)-D(182)-R(183) of CXCR4) which are components of the undecapeptidyl arch (UPA: from R(168) to C(178) in CCR5, from N(176) to C(186) in CXCR4) of extracellular loop 2 (ECL2) in chemokine receptors (CCR5 and CXCR4).
56 11478800 The antibody reacted with the cells separately expressing CCR5 or CXCR4, but not with those not expressing the coreceptors.
57 11478800 Moreover, the antibody markedly suppressed infection by X4, R5, or R5X4 virus in a dose-dependent manner in a new phenotypic assay for drug susceptibility of HIV-1 using CCR5-expressing Hela/CD4(+) cell clone 1-10 (MAGIC-5).
58 11559423 Continuous cultures of 18 isolates were established in the CCR5+/CXCR4+ cell line PM-1, and SI/NSI features of these viruses were confirmed by cell fusion assay with uninfected CD4+ T cell lines (PM-1, MT-2, H9, and SUP-T1).
59 11559423 The coreceptor usage of 18 isolates was investigated by infecting U87 cells transfected with CD4 and chemokine receptors, and we found that 11 isolates infected only CCR5+ cells, 3 only CXCR4+ cells, whereas 4 used both coreceptors.
60 11559423 Continuous cultures of 18 isolates were established in the CCR5+/CXCR4+ cell line PM-1, and SI/NSI features of these viruses were confirmed by cell fusion assay with uninfected CD4+ T cell lines (PM-1, MT-2, H9, and SUP-T1).
61 11559423 The coreceptor usage of 18 isolates was investigated by infecting U87 cells transfected with CD4 and chemokine receptors, and we found that 11 isolates infected only CCR5+ cells, 3 only CXCR4+ cells, whereas 4 used both coreceptors.
62 11602749 Human immunodeficiency virus (HIV) fusion and entry involves sequential interactions between the viral envelope protein, gp120, cell surface CD4, and a G-protein-coupled coreceptor.
63 11602749 In this study, we examined the disposition of these features during the fusion of HeLa cells expressing either HIV(HXB2) envelope (Env cells) or CXCR4 and CD4 (target cells).
64 11602749 Analyses of cells arrested by cooling to 4( degrees )C revealed that antibodies against the CD4-induced coreceptor-binding domain, i.e., 17b, 48d, and CG10, faintly react with Env cells even in the absence of target cell or soluble CD4 (sCD4) interactions.
65 11739668 Infection was inhibited by SDF-1 on cells expressing CD4 and CXCR4 for both viruses, whereas RANTES abolished infection of cells expressing CCR5 in addition to CD4 in studies of the RV expressing HIV-1(89.6) Env.
66 11788023 All six pseudoviruses were infectious and exhibited expected coreceptor usage phenotype in HOS-CD4 cells expressing either CCR5 or CXCR4.
67 11877292 The results show that a variety of differentiation molecules, proteins involved in the control of apoptosis, the B-cell transcription factors, positive regulatory domain I-binding factor 1/B lymphocyte-induced maturation protein 1 and B cell-specific activating protein and, at least partially, the chemokine receptor CXCR4 were expressed by human PCs following a gradient of increasing maturity in the direction: tonsil-->blood-->BM.
68 11902830 Mature DCs expressed significantly heightened levels of their antigen-presenting machinery (e.g., CD54, CD80, CD86) and numerous cytokines and chemokines/chemokine receptors (i.e., Flt-3L, G-CSF, IL-1alpha and -1beta, IL-6, IL-12, CCL-2, -3, -4, -5, -17, and -22, MIP-2, and CCR7) and were significantly better at inducing effector T cell responses in vitro.
69 11902830 Nevertheless, intermediate-maturity DCs expressed substantial levels of Flt-3L, IGF-1, IL-1alpha and -1beta, IL-6, CCL-2, -3, -4, -9/10, -17, and -22, MIP-2, osteopontin, CCR-1, -2, -5, and -7, and CXCR-4.
70 11983255 An increasing body of evidence supports the concept that the level of CCR5-binding chemokines (i.e., RANTES, MIP-1alpha and MIP-1beta) measured in vivo or ex vivo can provide an accurate correlate of natural or vaccine-induced protection from primate immunodeficiency viruses.
71 11983255 Chemokines that bind the major HIV coreceptors (i.e., CCR5 and CXCR4) are potent natural inhibitors of HIV, although a potential limitation to their therapeutic use is the risk of inducing inflammatory side-effects or of interfering with the physiology of the homeostatic chemokine system.
72 12072535 By contrast, these viruses are unchanged in their sensitivities to soluble CD4, the CXCR4 coreceptor ligand SDF-1alpha, and human anti-HIV immunoglobulin, reagents that impact the initial, receptor-induced conformational changes in the envelope glycoprotein.
73 12120995 Some retroviruses such as HIV-1 and HIV-2 utilize one receptor for high-affinity binding (CD4), and a separate coreceptor to mediate fusion of the viral envelope with the cell membrane (CCR5 or CXCR4).
74 12324710 We found that different strains of HIV have different ability to infect thymic epithelial cells; the ability to infect thymic epithelial cells may not be directly related to CCR5/CXCR4 usage.
75 12414953 Here we examined the disposition and antigenic nature of these structures during the HIV-mediated fusion of HeLa cells expressing either HIV(HXB2) envelope (Env cells) or CXCR4 and CD4 (target cells).
76 12462149 Subsequent interaction of the envelope protein (Env) with the CD4 receptor causes conformational changes that enable Env to interact with a coreceptor, generally the chemokine receptors CCR5 or CXCR4.
77 12462390 The differential usage of the two major HIV coreceptors, CCR5 and CXCR4, determines the biological diversity among HIV variants.
78 12462390 Most primary HIV strains use CCR5 as a coreceptor and thereby are sensitive to inhibition by the CCR5-ligand chemokines, RANTES, MIP-1alpha and MIP-1beta.
79 12462390 A smaller proportion of HIV isolates, commonly emerging in concomitance with the clinical progression toward AIDS, uses CXCR4 as a coreceptor and is inhibited by the CXCR4 ligand, SDF-1.
80 12462390 The high level of expresion of SDF-1 in the genital mucosa may help to explain the inefficient transmission of CXCR4-tropic HIV.
81 12462390 The differential usage of the two major HIV coreceptors, CCR5 and CXCR4, determines the biological diversity among HIV variants.
82 12462390 Most primary HIV strains use CCR5 as a coreceptor and thereby are sensitive to inhibition by the CCR5-ligand chemokines, RANTES, MIP-1alpha and MIP-1beta.
83 12462390 A smaller proportion of HIV isolates, commonly emerging in concomitance with the clinical progression toward AIDS, uses CXCR4 as a coreceptor and is inhibited by the CXCR4 ligand, SDF-1.
84 12462390 The high level of expresion of SDF-1 in the genital mucosa may help to explain the inefficient transmission of CXCR4-tropic HIV.
85 12462390 The differential usage of the two major HIV coreceptors, CCR5 and CXCR4, determines the biological diversity among HIV variants.
86 12462390 Most primary HIV strains use CCR5 as a coreceptor and thereby are sensitive to inhibition by the CCR5-ligand chemokines, RANTES, MIP-1alpha and MIP-1beta.
87 12462390 A smaller proportion of HIV isolates, commonly emerging in concomitance with the clinical progression toward AIDS, uses CXCR4 as a coreceptor and is inhibited by the CXCR4 ligand, SDF-1.
88 12462390 The high level of expresion of SDF-1 in the genital mucosa may help to explain the inefficient transmission of CXCR4-tropic HIV.
89 12504566 His PBMC resisted superinfection with CCR5, CXCR4, and dual-tropic HIV-1 strains, although highly purified CD4+ T cells supported infection, but without any visible cytopathic effect.
90 12504566 This activity was not mediated by several known chemokines or IFN-gamma, which were produced at high levels after PHA activation of his CD8+ T cells, indicating the action of other CAF-like CD8 factors.
91 12504566 Immunological mechanisms associated with this antiviral suppressive activity included vigorous Gag-specific helper T cell proliferative responses and high-level IFN-gamma release by both CD4 and CD8 T cells.
92 12547594 The results show that although cAMP does not stimulate full maturation of DCs it induces upregulation of the chemokine receptors CXCR4 and CCR7.
93 12799035 The expression of the chemokine receptor CXCR-4 and CCR-7 remained unaltered during cryopreservation and the migratory responsiveness towards MIP-3beta was unaltered as measured in a migration assay.
94 12879309 Polymorphism of human and primate RANTES, CX3CR1, CCR2 and CXCR4 genes with regard to HIV/SIV infection.
95 12879309 We have studied in non-human primates (chimpanzee, gorilla, gibbon, orang-utan, crab-eating and rhesus macaque, baboon and marmoset) the RANTES, CCR2 and CX3CR1 gene sequences in regions surrounding human mutations that were associated with susceptibility to HIV or AIDS progression: RANTES G-403A and C-28G, CCR2 V64I, CX3CR1 V249I and CX3CR1 T280M.
96 12960227 Surprisingly, lamina propria lymphocytes, not macrophages, express CCR5 and CXCR4 and support HIV-1 replication, implicating intestinal lymphocytes as the initial target cell in the intestinal mucosa.
97 12960237 Therapeutic agents that interfere with the binding of the HIV envelope glycoprotein gp120 to the CD4 receptor (e.g., PRO 542, PRO 2000, and CV-N) or the coreceptors CCR5 and CXCR4 (e.g., SCH-C and AMD3100) are briefly outlined in this review.
98 12963814 CD8+ T cell-mediated CXC chemokine receptor 4-simian/human immunodeficiency virus suppression in dually infected rhesus macaques.
99 12963814 We coinfected rhesus macaques with CXC chemokine receptor 4- and CC chemokine receptor 5-specific simian/human immunodeficiency viruses (SHIVs) to elucidate the basis for the early dominance of R5-tropic strains seen in HIV-infected humans.
100 12963814 CD8+ T cell-mediated CXC chemokine receptor 4-simian/human immunodeficiency virus suppression in dually infected rhesus macaques.
101 12963814 We coinfected rhesus macaques with CXC chemokine receptor 4- and CC chemokine receptor 5-specific simian/human immunodeficiency viruses (SHIVs) to elucidate the basis for the early dominance of R5-tropic strains seen in HIV-infected humans.
102 12969546 CD1a and CD1c cell sorting yields a homogeneous population of immature human Langerhans cells.
103 12969546 CD1c selection yielded a homogeneous population of pure and viable HLA-DR(+)/CD1a(+) DCs, with the ultrastructural features, surface antigen expression and cytokine profile, characteristic of epidermis-resident immature LCs.
104 12969546 Characterizing the cells in more detail, we could demonstrate for the first time that normal human LCs express CXCR4, CD40 ligand (CD40L), and Fas and Fas ligand (FasL).
105 12969546 LPS and IFN-omega stimulated the expression of the inflammatory cytokines TNF-alpha and IL-1beta, and there was secretion of IL-12p70 after CD40 ligation.
106 14505910 Purified complexes of HIV-1 envelope glycoproteins with CD4 and CCR5(CXCR4): production, characterization and immunogenicity.
107 14505910 To begin to evaluate their potential also as vaccine immunogens we produced relatively large amounts of complexes of purified recombinant soluble truncated Env, gp140(89.6) or gp120(89.6), with CD4 and CCR5 or CXCR4.
108 14505910 We found that gp140(gp120)-CD4-CCR5 complexes are stable and immunogenic in mice transgenic for human CD4 and CCR5.
109 14505910 Purified complexes of HIV-1 envelope glycoproteins with CD4 and CCR5(CXCR4): production, characterization and immunogenicity.
110 14505910 To begin to evaluate their potential also as vaccine immunogens we produced relatively large amounts of complexes of purified recombinant soluble truncated Env, gp140(89.6) or gp120(89.6), with CD4 and CCR5 or CXCR4.
111 14505910 We found that gp140(gp120)-CD4-CCR5 complexes are stable and immunogenic in mice transgenic for human CD4 and CCR5.
112 14579278 Mouse monoclonal antibodies (mAb) with kappaL chains were targeted to various chemokine receptors expressed on human monocytes or immature dendritic cells (DC), and proliferation of cloned human, DR4-restricted CD4+ T cells specific for mouse Ckappa(40-48) was measured.
113 14579278 When using monocytes as antigen-presenting cells, mAb specific for CCR1, CCR2, CCR5, and CXCR4 were 100-10,000-fold more efficient at inducing T cell proliferation when compared to isotype-matched control mAb on a per molecule basis.
114 14581570 Nine Envs used CCR5 as a coreceptor, one used CXCR4, and two used both CCR5 and CXCR4 in cell-to-cell fusion assays.
115 14581570 Eight Envs could also use CCR3, CCR8, GPR15, STRL33, Apj, and/or GPR1, but these coreceptors did not play a major role in virus entry into microglia.
116 14592822 Here, we report that Hsp70-like protein 1 (Hsp70L1), a novel HSP derived from human dendritic cells (DCs), has potent adjuvant effects that polarize responses toward Th1.
117 14592822 With a calculated molecular weight of 54.8 kDa, Hsp70L1 is smaller in size than Hsp70 but resembles it both structurally and functionally.
118 14592822 Hsp70L1 shares common receptors on DCs with Hsp70 and can interact with DCs, promoting DC maturation and stimulating secretion of the proinflammatory cytokines interleukin 12p70 (IL-12p70), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and the chemokines IP-10, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and normal T cell expressed and secreted (RANTES).
119 14592822 The induction of interferon-gamma-inducible protein 10 (IP-10) secretion by Hsp70L1 is not shared by Hsp70, and other functional differences include more potent stimulation of DC IL-12p70, CC-chemokine, and CCR7 and CXCR4 expression by Hsp70L1.
120 14657379 Here, we show that soluble suppressive factors are produced against CXCR4 and CCR5 isolates of HIV-1 during the primary immune response of human CD4+ T cells.
121 14657379 One anti-CXCR4 factor is macrophage-derived chemokine (chemokine ligand 22, CCL22), and anti-CCR5 factors include macrophage inflammatory protein-1 alpha (CCL3), macrophage inflammatory protein-1 beta (CCL4), and RANTES (regulated upon activation of normal T cells expressed and secreted) (CCL5).
122 14657379 Intracellular staining confirms that CD3+CD4+ T cells are the source of the prototype HIV-1-inhibiting chemokines CCL22 and CCL4.
123 15117454 Effects of human immunodeficiency virus type 1 infection on CCR5 and CXCR4 coreceptor expression on CD4 T lymphocyte subsets in infants and adolescents.
124 15117454 HIV-1 infection alters expression of CCR5 and CXCR4 on CD4 T cells in adults, although an effect by virus on expression of coreceptor genes in pediatric subjects is unknown.
125 15117454 We designed an exploratory study to evaluate surface expression of CXCR4 and CCR5 on CD45RA and CD45RO subsets of CD4 T lymphocytes from 17 HIV-1-infected infants and adolescents and 16 healthy age-matched individuals.
126 15117454 Among infected adolescents, CCR5 and CXCR4 expression was significantly increased on CD4 CD45RO T cells, while CXCR4 was diminished in the CD4 CD45RA subset.
127 15117454 The CD45RA CD45RO subset in culture expressed high levels of CD4, CXCR4, and CD69, an early activation marker, and was highly susceptible to HIV-1 infection and replication.
128 15117454 Effects of human immunodeficiency virus type 1 infection on CCR5 and CXCR4 coreceptor expression on CD4 T lymphocyte subsets in infants and adolescents.
129 15117454 HIV-1 infection alters expression of CCR5 and CXCR4 on CD4 T cells in adults, although an effect by virus on expression of coreceptor genes in pediatric subjects is unknown.
130 15117454 We designed an exploratory study to evaluate surface expression of CXCR4 and CCR5 on CD45RA and CD45RO subsets of CD4 T lymphocytes from 17 HIV-1-infected infants and adolescents and 16 healthy age-matched individuals.
131 15117454 Among infected adolescents, CCR5 and CXCR4 expression was significantly increased on CD4 CD45RO T cells, while CXCR4 was diminished in the CD4 CD45RA subset.
132 15117454 The CD45RA CD45RO subset in culture expressed high levels of CD4, CXCR4, and CD69, an early activation marker, and was highly susceptible to HIV-1 infection and replication.
133 15117454 Effects of human immunodeficiency virus type 1 infection on CCR5 and CXCR4 coreceptor expression on CD4 T lymphocyte subsets in infants and adolescents.
134 15117454 HIV-1 infection alters expression of CCR5 and CXCR4 on CD4 T cells in adults, although an effect by virus on expression of coreceptor genes in pediatric subjects is unknown.
135 15117454 We designed an exploratory study to evaluate surface expression of CXCR4 and CCR5 on CD45RA and CD45RO subsets of CD4 T lymphocytes from 17 HIV-1-infected infants and adolescents and 16 healthy age-matched individuals.
136 15117454 Among infected adolescents, CCR5 and CXCR4 expression was significantly increased on CD4 CD45RO T cells, while CXCR4 was diminished in the CD4 CD45RA subset.
137 15117454 The CD45RA CD45RO subset in culture expressed high levels of CD4, CXCR4, and CD69, an early activation marker, and was highly susceptible to HIV-1 infection and replication.
138 15117454 Effects of human immunodeficiency virus type 1 infection on CCR5 and CXCR4 coreceptor expression on CD4 T lymphocyte subsets in infants and adolescents.
139 15117454 HIV-1 infection alters expression of CCR5 and CXCR4 on CD4 T cells in adults, although an effect by virus on expression of coreceptor genes in pediatric subjects is unknown.
140 15117454 We designed an exploratory study to evaluate surface expression of CXCR4 and CCR5 on CD45RA and CD45RO subsets of CD4 T lymphocytes from 17 HIV-1-infected infants and adolescents and 16 healthy age-matched individuals.
141 15117454 Among infected adolescents, CCR5 and CXCR4 expression was significantly increased on CD4 CD45RO T cells, while CXCR4 was diminished in the CD4 CD45RA subset.
142 15117454 The CD45RA CD45RO subset in culture expressed high levels of CD4, CXCR4, and CD69, an early activation marker, and was highly susceptible to HIV-1 infection and replication.
143 15117454 Effects of human immunodeficiency virus type 1 infection on CCR5 and CXCR4 coreceptor expression on CD4 T lymphocyte subsets in infants and adolescents.
144 15117454 HIV-1 infection alters expression of CCR5 and CXCR4 on CD4 T cells in adults, although an effect by virus on expression of coreceptor genes in pediatric subjects is unknown.
145 15117454 We designed an exploratory study to evaluate surface expression of CXCR4 and CCR5 on CD45RA and CD45RO subsets of CD4 T lymphocytes from 17 HIV-1-infected infants and adolescents and 16 healthy age-matched individuals.
146 15117454 Among infected adolescents, CCR5 and CXCR4 expression was significantly increased on CD4 CD45RO T cells, while CXCR4 was diminished in the CD4 CD45RA subset.
147 15117454 The CD45RA CD45RO subset in culture expressed high levels of CD4, CXCR4, and CD69, an early activation marker, and was highly susceptible to HIV-1 infection and replication.
148 15161081 A, B, D, F and O clade gp 140s were found to be multimeric, bind to a panel of defined env-specific monoclonal antibodies and interact with CD4 and CXCR4, demonstrating correct folding.
149 15161081 The binding of gp140 to soluble and cell-surface CD4 and CXCR4 is related to the degree of oligomerisation.
150 15161081 A, B, D, F and O clade gp 140s were found to be multimeric, bind to a panel of defined env-specific monoclonal antibodies and interact with CD4 and CXCR4, demonstrating correct folding.
151 15161081 The binding of gp140 to soluble and cell-surface CD4 and CXCR4 is related to the degree of oligomerisation.
152 15297611 By using small-molecule competitors specific for CCR5 and CXCR4 in ex vivo assays, we found that highly pathogenic SHIV(DH12R) exclusively uses CXCR4 for infection of rhesus peripheral blood mononuclear cells, whereas SIV(mac239) and SIV(smE543) use CCR5 for entry into the same cells.
153 15297611 During the period of peak virus production in SHIV(DH12R)- or SHIV(89.6P)-infected rhesus monkeys, massive elimination of CXCR4(+) naïve CD4(+) T cells occurred.
154 15297611 In contrast, circulating CCR5(+) memory CD4(+) T cells were selectively depleted in rapidly progressing SIV-infected monkeys.
155 15297611 By using small-molecule competitors specific for CCR5 and CXCR4 in ex vivo assays, we found that highly pathogenic SHIV(DH12R) exclusively uses CXCR4 for infection of rhesus peripheral blood mononuclear cells, whereas SIV(mac239) and SIV(smE543) use CCR5 for entry into the same cells.
156 15297611 During the period of peak virus production in SHIV(DH12R)- or SHIV(89.6P)-infected rhesus monkeys, massive elimination of CXCR4(+) naïve CD4(+) T cells occurred.
157 15297611 In contrast, circulating CCR5(+) memory CD4(+) T cells were selectively depleted in rapidly progressing SIV-infected monkeys.
158 15479838 Although CXCR4-tropic virus is more cytopathic for T cells, CCR5-tropic strains are transmitted more frequently in humans for reasons that are not understood.
159 15479838 Infected immature mDCs differentiated normally and were found to enhance CCR5-tropic but not CXCR4-tropic virus infection of T cells even in the continuous presence of neutralizing antibodies.
160 15479838 Although CXCR4-tropic virus is more cytopathic for T cells, CCR5-tropic strains are transmitted more frequently in humans for reasons that are not understood.
161 15479838 Infected immature mDCs differentiated normally and were found to enhance CCR5-tropic but not CXCR4-tropic virus infection of T cells even in the continuous presence of neutralizing antibodies.
162 15507523 On days 6 and 7 after immunization, CD19(+)/CD27(high)/intracellular immunoglobulin G(high) (IgG(high))/HLA-DR(high)/CD38(high)/CD20(-)/CD95(+) tetanus toxin-specific antibody-secreting plasma blasts were released in large numbers from the secondary lymphoid organs into the blood.
163 15507523 These cells show chemotactic responsiveness toward ligands for CXCR3 and CXCR4, probably guiding them to the bone marrow or inflamed tissue.
164 15507523 At the same time, a population of CD19(+)/CD27(high)/intracellular IgG(high)/HLA-DR(low)/CD38(+)/CD20(-)/CD95(+) cells appeared in the blood in large numbers.
165 15725757 Thus the sequence of V3, directly or indirectly, can determine which coreceptor (CCR5 or CXCR4) is used to trigger the fusion potential of the Env complex, and hence which cells the virus can infect.
166 15857994 Syncytium formation in MT-2 cells and CCR5 or CXCR4 coreceptor usage were determined for all isolates.
167 16114988 J558 cells gave rise to a 100% tumor incidence, whereas SDF-1-expressing J558/SDF-1 tumors invariably regressed in BALB/c mice and became infiltrated with CD4(+) and CD8(+) T cells.
168 16114988 Regression of the J558/SDF-1 tumors was dependent on both CD4(+) and CD8(+) T-cells.
169 16114988 Our data also indicate that TIT cells containing both CD4(+) and CD8(+) T-cells within J558/SDF-1 tumors express the SDF-1 receptor CXCR4, and that SDF-1 specifically chemoattracts these cells in vitro.
170 16114988 Furthermore, immunization of mice with engineered J558/SDF-1 cells elicited the most potent protective immunity against 0.5 x 10(6) cells J558 tumor challenge in vivo, compared to immunization with the J558 alone, and this antitumor immunity mediated by J558/SDF-1 tumor cell vaccination in vivo appeared to be dependent on CD8(+) CTL.
171 16248793 HIV-1 cell entry is mediated by sequential interactions of the envelope protein gp120 with the receptor CD4 and a coreceptor, usually CCR5 or CXCR4, depending on the individual virion.
172 16272569 A cyclic chimeric dodecapeptide (cCD) mimicking the conformation-specific domains of CCR5 and CXCR4 was prepared in which Gly-Asp links the amino and carboxyl termini of two combined pentapeptides (S169-G173 of CCR5; E179-R183 of CXCR4) derived from human immunodeficiency virus type-1 (HIV-1) coreceptors.
173 16272569 The immunization of Balb/c mice with cCD conjugated with a multiple-antigen peptide (cCD-MAP) induced seven cCD-specific monoclonal antibodies (mAbs, CPMAb-I to -VII) that reacted with native CCR5 and CXCR4.
174 16272569 A cyclic chimeric dodecapeptide (cCD) mimicking the conformation-specific domains of CCR5 and CXCR4 was prepared in which Gly-Asp links the amino and carboxyl termini of two combined pentapeptides (S169-G173 of CCR5; E179-R183 of CXCR4) derived from human immunodeficiency virus type-1 (HIV-1) coreceptors.
175 16272569 The immunization of Balb/c mice with cCD conjugated with a multiple-antigen peptide (cCD-MAP) induced seven cCD-specific monoclonal antibodies (mAbs, CPMAb-I to -VII) that reacted with native CCR5 and CXCR4.
176 16280169 Plasmablasts but not mature plasma cells are attracted by the ligands for the chemokine receptors CXCR4 and CXCR3.
177 16280169 While CXCR4 and its cognate ligand is important for plasma cell homing to the bone marrow, CXCR3 and its ligand IP10 are likely to be involved in attracting them to inflamed tissue.
178 16280169 Plasmablasts but not mature plasma cells are attracted by the ligands for the chemokine receptors CXCR4 and CXCR3.
179 16280169 While CXCR4 and its cognate ligand is important for plasma cell homing to the bone marrow, CXCR3 and its ligand IP10 are likely to be involved in attracting them to inflamed tissue.
180 16387698 Therefore, fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors.
181 16387698 The best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor, and (2) binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5.
182 16387698 The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O.
183 16387698 Therefore, fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors.
184 16387698 The best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor, and (2) binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5.
185 16387698 The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O.
186 16387698 Therefore, fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors.
187 16387698 The best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor, and (2) binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5.
188 16387698 The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O.
189 16437164 To initiate infection, the HIV-1 external envelope glycoprotein, gp120, sequentially interacts with two cellular receptors, CD4 and a chemokine receptor (or coreceptor) like CCR5 or CXCR4.
190 16437164 The differential use of CCR5 and CXCR4 defines three HIV-1 biological variants (R5, R5X4, X4), which vary in their prevalence during the disease course.
191 16437164 To initiate infection, the HIV-1 external envelope glycoprotein, gp120, sequentially interacts with two cellular receptors, CD4 and a chemokine receptor (or coreceptor) like CCR5 or CXCR4.
192 16437164 The differential use of CCR5 and CXCR4 defines three HIV-1 biological variants (R5, R5X4, X4), which vary in their prevalence during the disease course.
193 16493048 It has been demonstrated that T cells are repelled by high concentrations of the chemokine CXCL12 via a concentration-dependent and CXCR4 receptor-mediated mechanism, termed chemorepulsion or fugetaxis.
194 16493048 Early recruitment of adoptively transferred OVA-specific CTL into B16/OVA tumors expressing high levels of CXCL12 was significantly reduced in comparison to B16/OVA tumors, and this reduction was reversed when tumor-specific CTLs were pretreated with the specific CXCR4 antagonist, AMD3100.
195 16493048 Expression of high levels of CXCL12 by B16/OVA cells significantly reduced CTL colocalization with and killing of target cells in vitro in a CXCR4-dependent manner.
196 16493048 It has been demonstrated that T cells are repelled by high concentrations of the chemokine CXCL12 via a concentration-dependent and CXCR4 receptor-mediated mechanism, termed chemorepulsion or fugetaxis.
197 16493048 Early recruitment of adoptively transferred OVA-specific CTL into B16/OVA tumors expressing high levels of CXCL12 was significantly reduced in comparison to B16/OVA tumors, and this reduction was reversed when tumor-specific CTLs were pretreated with the specific CXCR4 antagonist, AMD3100.
198 16493048 Expression of high levels of CXCL12 by B16/OVA cells significantly reduced CTL colocalization with and killing of target cells in vitro in a CXCR4-dependent manner.
199 16493048 It has been demonstrated that T cells are repelled by high concentrations of the chemokine CXCL12 via a concentration-dependent and CXCR4 receptor-mediated mechanism, termed chemorepulsion or fugetaxis.
200 16493048 Early recruitment of adoptively transferred OVA-specific CTL into B16/OVA tumors expressing high levels of CXCL12 was significantly reduced in comparison to B16/OVA tumors, and this reduction was reversed when tumor-specific CTLs were pretreated with the specific CXCR4 antagonist, AMD3100.
201 16493048 Expression of high levels of CXCL12 by B16/OVA cells significantly reduced CTL colocalization with and killing of target cells in vitro in a CXCR4-dependent manner.
202 16500130 Dendritic cells express CCR7 and migrate in response to CCL19 (MIP-3beta) after exposure to Helicobacter pylori.
203 16500130 Migration of DC to lymph nodes is regulated by chemokine receptor CCR7, expressed on mature DC, and the CCR7 ligands CCL19 and CCL21.
204 16500130 Stimulation with H. pylori induced maturation of DC, i.e. up-regulation of the chemokine receptors CCR7 and CXCR4 and the maturation markers HLA-DR, CD80 and CD86.
205 16500130 Despite low surface expression of CCR7 protein following stimulation with H. pylori compared to E. coli, the DC migrated equally well towards CCL19 after stimulation with both bacteria.
206 16672543 HIV enters cells via the CD4 molecule, chemokine co-receptors (CXCR4, CCR5), and other cell-surface proteins.
207 16699036 An antibody response capable of neutralizing not only homologous but also heterologous forms of the CXCR4-tropic human immunodeficiency virus type 1 (HIV-1) MNp and CCR5-tropic primary isolate HIV-1 JR-CSF was achieved through sequential immunization with a combination of synthetic peptides representing HIV-1 Env V3 sequences from field and laboratory HIV-1 clade B isolates.
208 16787241 Entry of HIV-1 into target cells involves interactions of the viral envelope protein (Env) with CD4 and a coreceptor, usually CCR5 or CXCR4.
209 16787246 Others target the HIV coreceptors CCR5 and CXCR4, and are now in clinical trials.
210 16787246 Also under development are novel agents that target the HIV integrase and HIV regulatory gene products as well as immunomodulators such as IL-12 and IL-2.
211 16848274 Since their discovery in 1996, the two main coreceptors used by human immunodeficiency virus type 1 (HIV-1) to enter human cells (CCR5 and CXCR4) have been the subject of numerous scientific articles.
212 16848274 Therefore, in addition to providing a brief update of the most important aspects described above, we discuss here how an accurate quantification of HIV coreceptor usage is essential for the successful management of HIV-infected individuals in this new era of entry inhibitors, mainly CCR5- or CXCR4-antagonists.
213 16848274 Since their discovery in 1996, the two main coreceptors used by human immunodeficiency virus type 1 (HIV-1) to enter human cells (CCR5 and CXCR4) have been the subject of numerous scientific articles.
214 16848274 Therefore, in addition to providing a brief update of the most important aspects described above, we discuss here how an accurate quantification of HIV coreceptor usage is essential for the successful management of HIV-infected individuals in this new era of entry inhibitors, mainly CCR5- or CXCR4-antagonists.
215 16920175 Viral evolution in macaques coinfected with CCR5- and CXCR4-tropic SHIVs in the presence or absence of vaccine-elicited anti-CCR5 SHIV neutralizing antibodies.
216 16920175 These findings provide new insights into the dynamic interaction of CCR5- and CXCR4-tropic HIV isolates that are potentially relevant in better understanding HIV-mediated pathogenesis.
217 16920175 Viral evolution in macaques coinfected with CCR5- and CXCR4-tropic SHIVs in the presence or absence of vaccine-elicited anti-CCR5 SHIV neutralizing antibodies.
218 16920175 These findings provide new insights into the dynamic interaction of CCR5- and CXCR4-tropic HIV isolates that are potentially relevant in better understanding HIV-mediated pathogenesis.
219 16923919 HIV-1 infection of cells is mediated by engagement between viral envelope glycoproteins (Env) and a receptor complex comprising CD4 and one of two chemokine receptors, CCR5 and CXCR4, expressed on the surface of target cells.
220 16923919 Most CD4+-transformed T cell lines express only CXCR4, but primary lymphocytes and macrophages, the main cellular targets for infection in vivo, express both coreceptors.
221 16923919 HIV-1 infection of cells is mediated by engagement between viral envelope glycoproteins (Env) and a receptor complex comprising CD4 and one of two chemokine receptors, CCR5 and CXCR4, expressed on the surface of target cells.
222 16923919 Most CD4+-transformed T cell lines express only CXCR4, but primary lymphocytes and macrophages, the main cellular targets for infection in vivo, express both coreceptors.
223 17068156 Noninfectious papilloma virus-like particles inhibit HIV-1 replication: implications for immune control of HIV-1 infection by IL-27.
224 17068156 Recent studies demonstrate that VLPs bind to dendritic cells and induce the expression of antiviral cytokines such as interferon-alpha (IFN-alpha), interleukin-10 (IL-10) and IFN-gamma.
225 17068156 Here, we show that VLPs suppress the replication of both X4 and R5 HIV-1 without affecting the expression of CD4, CXCR4, and CCR5.
226 17068156 VLPs induced the genes associated with IFN induction, immune responses, and antiviral responses, among with the recently described cytokine IL-27.
227 17068156 Subsequently, IL-27 was found to be a potent inhibitor of HIV-1 replication in PBMCs, CD4+ T cells, and macrophages.
228 17068156 Taken together, our studies identify a novel role of IL-27 in restricting HIV-1 replication and suggest that further examination of the inhibitory property of IL-27 may pave the way for a novel therapy for HIV-1 infection.
229 17093191 Phospholipase A2 (PLA2) proteins affect cellular activation, signal transduction, and possibly innate immunity.
230 17093191 Catalytic function was required for antiviral activity, and the target cells of infection were unaffected. sPLA2-X potently reduced gene transfer of HIV-1 Env-pseudotyped lentivirus vectors and inhibited the replication of both CCR5- and CXCR4-tropic HIV-1 in human CD4+ T cells.
231 17241712 The vaccine has been prepared by mixing and incubating Env-PVs, with incorporated fusion-defective Env, with PVs, which have incorporated functional CD4 and CXCR4 proteins.
232 17241712 In all cases, antibody binding required an interaction of the Env-PVs with CD4 whereas CXCR4 was dispensible.
233 17241712 The vaccine has been prepared by mixing and incubating Env-PVs, with incorporated fusion-defective Env, with PVs, which have incorporated functional CD4 and CXCR4 proteins.
234 17241712 In all cases, antibody binding required an interaction of the Env-PVs with CD4 whereas CXCR4 was dispensible.
235 17277122 Human immature dendritic cells (DCs) cultured in the presence of c-di-GMP showed increased expression of costimulatory molecules CD80/CD86 and maturation marker CD83, increased MHC class II and cytokines and chemokines such as IL-12, IFN-gamma, IL-8, MCP-1, IFN-gamma-inducible protein 10, and RANTES, and altered expression of chemokine receptors including CCR1, CCR7, and CXCR4. c-di-GMP-matured DCs demonstrated enhanced T cell stimulatory activity. c-di-GMP activated p38 MAPK in human DCs and ERK phosphorylation in human macrophages. c-di-GMP is stable in human serum.
236 17460054 CCR5 or CXCR4 coreceptor usage was determined by production of recombinant viral particles, followed by single-cycle infection assays of indicator cell lines, using the tropism recombinant test.
237 17584153 Human immunodeficiency virus type 1 (HIV-1) requires a chemokine receptor (CCR5 or CXCR4) as a coreceptor not only for initiate viral entry but also protecting highly conserved neutralization epitopes from the attack of neutralizing antibodies.
238 17584153 Here, we propose that chemokine receptors are attractive targets of vaccine development because their structures are highly conserved and that our synthetic cycloimmunogens can mimic conformational-specific epitopes of undecapeptidyl arches (UPAs: R(168)-C(178) in CCR5, N(176)-C(186) in CXCR4) and be useful for HIV-1 novel vaccine development.
239 17584153 Human immunodeficiency virus type 1 (HIV-1) requires a chemokine receptor (CCR5 or CXCR4) as a coreceptor not only for initiate viral entry but also protecting highly conserved neutralization epitopes from the attack of neutralizing antibodies.
240 17584153 Here, we propose that chemokine receptors are attractive targets of vaccine development because their structures are highly conserved and that our synthetic cycloimmunogens can mimic conformational-specific epitopes of undecapeptidyl arches (UPAs: R(168)-C(178) in CCR5, N(176)-C(186) in CXCR4) and be useful for HIV-1 novel vaccine development.
241 17609282 Entry of human immunodeficiency virus type 1 (HIV-1) and HIV-2 requires interactions between the envelope glycoprotein (Env) on the virus and CD4 and a chemokine receptor, either CCR5 or CXCR4, on the cell surface.
242 17609282 The V3 loop of the HIV gp120 glycoprotein plays a critical role in this process, determining tropism for CCR5- or CXCR4-expressing cells, but details of how V3 interacts with these receptors have not been defined.
243 17609282 V3-deleted Envs exhibited tropism for both CCR5- and CXCR4-expressing cells, suggesting that domains on the gp120 core were mediating interactions with determinants shared by both coreceptors.
244 17609282 Remarkably, HIV-2 Envs with V3 deletions became resistant to small-molecule inhibitors of CCR5 and CXCR4, suggesting that these drugs inhibit wild-type viruses by disrupting a specific V3 interaction with the coreceptor.
245 17609282 Entry of human immunodeficiency virus type 1 (HIV-1) and HIV-2 requires interactions between the envelope glycoprotein (Env) on the virus and CD4 and a chemokine receptor, either CCR5 or CXCR4, on the cell surface.
246 17609282 The V3 loop of the HIV gp120 glycoprotein plays a critical role in this process, determining tropism for CCR5- or CXCR4-expressing cells, but details of how V3 interacts with these receptors have not been defined.
247 17609282 V3-deleted Envs exhibited tropism for both CCR5- and CXCR4-expressing cells, suggesting that domains on the gp120 core were mediating interactions with determinants shared by both coreceptors.
248 17609282 Remarkably, HIV-2 Envs with V3 deletions became resistant to small-molecule inhibitors of CCR5 and CXCR4, suggesting that these drugs inhibit wild-type viruses by disrupting a specific V3 interaction with the coreceptor.
249 17609282 Entry of human immunodeficiency virus type 1 (HIV-1) and HIV-2 requires interactions between the envelope glycoprotein (Env) on the virus and CD4 and a chemokine receptor, either CCR5 or CXCR4, on the cell surface.
250 17609282 The V3 loop of the HIV gp120 glycoprotein plays a critical role in this process, determining tropism for CCR5- or CXCR4-expressing cells, but details of how V3 interacts with these receptors have not been defined.
251 17609282 V3-deleted Envs exhibited tropism for both CCR5- and CXCR4-expressing cells, suggesting that domains on the gp120 core were mediating interactions with determinants shared by both coreceptors.
252 17609282 Remarkably, HIV-2 Envs with V3 deletions became resistant to small-molecule inhibitors of CCR5 and CXCR4, suggesting that these drugs inhibit wild-type viruses by disrupting a specific V3 interaction with the coreceptor.
253 17609282 Entry of human immunodeficiency virus type 1 (HIV-1) and HIV-2 requires interactions between the envelope glycoprotein (Env) on the virus and CD4 and a chemokine receptor, either CCR5 or CXCR4, on the cell surface.
254 17609282 The V3 loop of the HIV gp120 glycoprotein plays a critical role in this process, determining tropism for CCR5- or CXCR4-expressing cells, but details of how V3 interacts with these receptors have not been defined.
255 17609282 V3-deleted Envs exhibited tropism for both CCR5- and CXCR4-expressing cells, suggesting that domains on the gp120 core were mediating interactions with determinants shared by both coreceptors.
256 17609282 Remarkably, HIV-2 Envs with V3 deletions became resistant to small-molecule inhibitors of CCR5 and CXCR4, suggesting that these drugs inhibit wild-type viruses by disrupting a specific V3 interaction with the coreceptor.
257 17983270 Gp120 from the HIV-1 strain JR-FL induced IL-10 expression in MDDCs from 62% of donors, via a mannose C-type lectin receptor(s) (MCLR).
258 17983270 The mannose-binding protein cyanovirin-N, the 2G12 mAb to a mannose-dependent gp120 epitope, and MCLR-specific mAbs inhibited IL-10 expression, as did enzymatic removal of gp120 mannose moieties, whereas inhibitors of signaling via CD4, CCR5, or CXCR4 were ineffective.
259 17983270 Gp120-stimulated IL-10 production correlated with DC-SIGN expression on the cells, and involved the ERK signaling pathway.
260 18209057 Ag-specific ASCs from the colon migrated to SDF-1alpha/CXCL12 and mucosae-associated epithelial chemokine/CCL28, suggesting that CXCR4(+) and/or CCR10(+) IgA ASCs found in the large intestine after s.c.
261 18209057 In the colonic patches-null mice, IgA ASCs in the large intestine were completely depleted.
262 18209057 Furthermore, the accumulation of IgA ASCs in the colonic patches by inhibition of their migration with FTY720 revealed that colonic patches are the IgA class-switching site after s.c.
263 18209057 -IR induced numbers of Ag-specific IgA ASCs in the large intestine of TLR2(-/-), TLR4(-/-), MyD88(-/-), and TRIF(-/-) mice that were comparable with those of wild-type mice.
264 18209074 In prior studies, we show that naturally occurring IgM anti-leukocyte autoantibodies (IgM-ALA) bind to CD3, CD4, CCR5, and CXCR4 receptors.
265 18449216 Membrane-anchored C-peptides (for example, maC46) derived from human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41 effectively inhibit HIV-1 entry in cell lines and primary human CD4+ cells in vitro.
266 18449216 Depletion of CD8+ T cells from PBMCs enhanced the yield of maC46-transduced CD4+ T cells.
267 18449216 Supplementation with interleukin-2 (IL-2) increased transduction efficiency, whereas IL-7 and/or IL-15 provided no additional benefit.
268 18449216 Phenotypic analysis showed that maC46-transduced and expanded cells were predominantly central memory CD4+ T cells that expressed low levels of CCR5 and slightly elevated levels of CD62L, beta7-integrin and CXCR4.
269 18594881 The HIV-1 gp120 exterior envelope glycoprotein undergoes a series of conformational rearrangements while sequentially interacting with the receptor CD4 and the coreceptor CCR5 or CXCR4 on the surface of host cells to initiate virus entry.
270 19058828 In contrast, HIV-1 isolates from AIDS patients showed high replication kinetics, used both CCR5 and CXCR4 co-receptors and induced syncytium formation.
271 19275640 Although the role of chemokine receptors (CKRs) in cancer biology is a relatively new field of study, a growing body of data suggest that a number of CKRs, including CXCR4, CCR4, CCR7, and CCR10, may play diverse of roles in cancer growth, cancer metastasis, cancer angiogenesis, or the composition of the cancer microenvironment.
272 19688091 This clone demonstrated robust viral propagation and profound syncytium formation in CD4+, CXCR4-expressing human glioma NP-2 cells, indicating that p05MYKL045.1 is a CXCR4-using virus.
273 19954551 While most of the sequences suggested CCR5 co-receptor usage, one subtype C sample clearly indicated CXCR4 usage.
274 20382859 Phenotypic EPC populations enumerated by flow cytometry [CD34(+)VEGF receptor (VEGF)R-2(+)CD133(+), CD14(+)VEGFR-2(+)Tie2(+), CD45(-)CD34(+), as a surrogate for late outgrowth EPCs, and CD34(+)CXCR-4(+)], EC-CFUs, and serum cytokine concentrations (high sensitivity C-reactive protein, IL-6, and stromal-derived factor-1) were quantified during the first 7 days.
275 20382859 Vaccination increased circulating leukocyte (9.8 + or - 0.6 vs. 5.1 + or - 0.2 x 10(9) cells/l, P < 0.0001), serum IL-6 [0.95 (0-1.7) vs. 0 (0-0) ng/l, P = 0.016], and VEGF-A [60 (45-94) vs. 43 (21-64) pg/l, P = 0.006] concentrations at 6 h and serum high sensitivity C-reactive protein at 24 h [2.7 (1.4-3.6) vs. 0.4 (0.2-0.8) mg/l, P = 0.037].
276 20382859 Vaccination caused a 56.7 + or - 7.6% increase in CD14(+) cells at 6 h (P < 0.001) and a 22.4 + or - 6.9% increase in CD34(+) cells at 7 days (P = 0.04).
277 20463101 Analytical and biological considerations in the measurement of cell-associated CCR5 and CXCR4 mRNA and protein.
278 20463101 The accurate measurement of T cell-associated CC chemokine receptor type 5 (CCR5) and CXC chemokine receptor type 4 (CXCR4) expression, including expression of CCR5 and CXCR4 mRNA as an immune measure of immunologic response to highly active antiretroviral therapy (HAART) and newer agents, including entry inhibitors, is essential.
279 20463101 Procedural methods are described that allow for the optimal measurement of naïve and memory T-helper cell CCR5 and CXCR4 expression as well as the quantitation of CCR5 and CXCR4 mRNA.
280 20463101 Analytical and biological considerations in the measurement of cell-associated CCR5 and CXCR4 mRNA and protein.
281 20463101 The accurate measurement of T cell-associated CC chemokine receptor type 5 (CCR5) and CXC chemokine receptor type 4 (CXCR4) expression, including expression of CCR5 and CXCR4 mRNA as an immune measure of immunologic response to highly active antiretroviral therapy (HAART) and newer agents, including entry inhibitors, is essential.
282 20463101 Procedural methods are described that allow for the optimal measurement of naïve and memory T-helper cell CCR5 and CXCR4 expression as well as the quantitation of CCR5 and CXCR4 mRNA.
283 20463101 Analytical and biological considerations in the measurement of cell-associated CCR5 and CXCR4 mRNA and protein.
284 20463101 The accurate measurement of T cell-associated CC chemokine receptor type 5 (CCR5) and CXC chemokine receptor type 4 (CXCR4) expression, including expression of CCR5 and CXCR4 mRNA as an immune measure of immunologic response to highly active antiretroviral therapy (HAART) and newer agents, including entry inhibitors, is essential.
285 20463101 Procedural methods are described that allow for the optimal measurement of naïve and memory T-helper cell CCR5 and CXCR4 expression as well as the quantitation of CCR5 and CXCR4 mRNA.
286 20548033 We asked whether the efficacy of dendritic cell (DC) vaccination with the renal cell carcinoma Ags MAGE-A9 (MAGE9) and G250 could be strengthened by covaccination with the renal cell carcinoma autoantigen GOLGA4.
287 20548033 Autoantigen covaccination significantly strengthened tumor Ag-specific CD4(+) and CD8(+) T cell expansion, particularly in peptide-loaded DC-vaccinated mice.
288 20548033 Covaccination was accompanied by an increase in inflammatory cytokines, boosted IL-12 and IFN-gamma expression, and promoted a high tumor Ag-specific CTL response.
289 20548033 Concomitant autoantigen vaccination also supported CCR6, CXCR3, and CXCR4 upregulation and T cell recruitment into the tumor.
290 20622876 Binding of the third variable region (V3) of the HIV-1 envelope glycoprotein gp120 to the cell-surface coreceptors CCR5 or CXCR4 during viral entry suggests that there are conserved structural elements in this sequence-variable region.
291 21068257 We utilized a green fluorescent protein (GFP)-expressing proviral construct pseudotyped with CCR5-tropic or CXCR4-tropic envelope to compare viral entry using a fluorescence resonance energy transfer-based, single-round virus-cell fusion assay.
292 21093412 HIV-1 Nef is a key factor for pathogenesis and is known to down-regulate functionally important molecules, including viral entry co-receptor CCR5 and CXCR4, from the surface of HIV-infected cells.
293 21106806 A small subset of human immunodeficiency virus type 1 (HIV-1)-infected, therapy-naive individuals--referred to as long-term non-progressors (LTNPs)--maintain a favourable course of infection, often being asymptomatic for many years with high CD4(+) and CD8(+) T-cell counts (>500 cells  μl(-1)) and low plasma HIV-RNA levels (<10 ,000 copies ml(-1)).
294 21106806 Studies have also shown that some LTNPs have unique genetic advantages, including heterozygosity for the CCR5-Δ32 polymorphism, and have been found with excitatory mutations that upregulate the production of the chemokines that competitively inhibit HIV-1 binding to CCR5 or CXCR4.
295 21106806 Lastly, immunological factors are crucial for providing LTNPs with a natural form of control, the most important being robust HIV-specific CD4(+) and CD8(+) T-cell responses that correlate with lower viral loads.
296 21106806 Many LTNPs carry the HLA class I B57 allele that enhances presentation of antigenic peptides on the surface of infected CD4(+) cells to cytotoxic CD8(+) T cells.
297 21128884 HIV utilizes the CD4 receptor and a range of 7 transmembrane chemokine coreceptors for cell entry, specifically CCR5 and CXCR4.
298 21128884 Furthermore, a large array of other receptors, other than CD4, CCR5 and/or CXCR4 can interact with HIV with consequences for HIV tranmssion as well as disease progression.
299 21128884 HIV utilizes the CD4 receptor and a range of 7 transmembrane chemokine coreceptors for cell entry, specifically CCR5 and CXCR4.
300 21128884 Furthermore, a large array of other receptors, other than CD4, CCR5 and/or CXCR4 can interact with HIV with consequences for HIV tranmssion as well as disease progression.
301 21469117 Here, we show that IL-4 and IL-13 production is NF-κB1-dependent in mouse OVA-specific CD4(+) (OTII) T cells responding to alum-precipitated OVA (alumOVA) immunization.
302 21469117 More surprisingly, we found that NF-κB1 deficiency in OTII cells also selectively impairs their CXCR5 induction by alumOVA without affecting upregulation of BCL6, IL-21, OX40 and CXCR4 mRNA and PD-1 protein.
303 21469117 The selective effects of NF-κB1-deficiency on Th2 and follicular helper T cell induction do not appear to be due to altered expression of the Th2-associated transcription factors - GATA-3, c-Maf and Ikaros.
304 21469117 Altogether, these results suggest that NF-κB1 regulates the expression of CXCR5 on CD4(+) T cells primed in vivo, and thus selectively controls the T-cell-dependent germinal center component of B-cell response to alumOVA.
305 21742774 CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer.
306 21742774 The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human cancers, including ovarian cancer, in which they are associated with disease progression at the levels of tumor cell proliferation, invasion, and angiogenesis.
307 21742774 Here, we used an immunocompetent mouse model of intraperitoneal papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4 axis in ovarian cancer has multimodal effects on tumor pathogenesis associated with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1 cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in vitro, and tumor growth in vivo.
308 21742774 In addition, the selective effect of CXCR4 antagonism on intratumoral Tregs was associated with both higher CXCR4 expression and increased chemotactic responses to CXCL12, a finding that was also confirmed in a melanoma model.
309 21742774 Together, our findings reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4 as a therapeutic target in this disease.
310 21742774 CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer.
311 21742774 The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human cancers, including ovarian cancer, in which they are associated with disease progression at the levels of tumor cell proliferation, invasion, and angiogenesis.
312 21742774 Here, we used an immunocompetent mouse model of intraperitoneal papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4 axis in ovarian cancer has multimodal effects on tumor pathogenesis associated with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1 cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in vitro, and tumor growth in vivo.
313 21742774 In addition, the selective effect of CXCR4 antagonism on intratumoral Tregs was associated with both higher CXCR4 expression and increased chemotactic responses to CXCL12, a finding that was also confirmed in a melanoma model.
314 21742774 Together, our findings reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4 as a therapeutic target in this disease.
315 21742774 CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer.
316 21742774 The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human cancers, including ovarian cancer, in which they are associated with disease progression at the levels of tumor cell proliferation, invasion, and angiogenesis.
317 21742774 Here, we used an immunocompetent mouse model of intraperitoneal papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4 axis in ovarian cancer has multimodal effects on tumor pathogenesis associated with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1 cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in vitro, and tumor growth in vivo.
318 21742774 In addition, the selective effect of CXCR4 antagonism on intratumoral Tregs was associated with both higher CXCR4 expression and increased chemotactic responses to CXCL12, a finding that was also confirmed in a melanoma model.
319 21742774 Together, our findings reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4 as a therapeutic target in this disease.
320 21742774 CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer.
321 21742774 The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human cancers, including ovarian cancer, in which they are associated with disease progression at the levels of tumor cell proliferation, invasion, and angiogenesis.
322 21742774 Here, we used an immunocompetent mouse model of intraperitoneal papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4 axis in ovarian cancer has multimodal effects on tumor pathogenesis associated with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1 cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in vitro, and tumor growth in vivo.
323 21742774 In addition, the selective effect of CXCR4 antagonism on intratumoral Tregs was associated with both higher CXCR4 expression and increased chemotactic responses to CXCL12, a finding that was also confirmed in a melanoma model.
324 21742774 Together, our findings reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4 as a therapeutic target in this disease.
325 21742774 CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer.
326 21742774 The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human cancers, including ovarian cancer, in which they are associated with disease progression at the levels of tumor cell proliferation, invasion, and angiogenesis.
327 21742774 Here, we used an immunocompetent mouse model of intraperitoneal papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4 axis in ovarian cancer has multimodal effects on tumor pathogenesis associated with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1 cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in vitro, and tumor growth in vivo.
328 21742774 In addition, the selective effect of CXCR4 antagonism on intratumoral Tregs was associated with both higher CXCR4 expression and increased chemotactic responses to CXCL12, a finding that was also confirmed in a melanoma model.
329 21742774 Together, our findings reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4 as a therapeutic target in this disease.
330 21835785 The great majority of human immunodeficiency virus type 1 (HIV-1) strains enter CD4+ target cells by interacting with one of two coreceptors, CCR5 or CXCR4.
331 21835785 Here we describe a transmitted/founder (T/F) virus (ZP6248) that was profoundly impaired in its ability to utilize CCR5 and CXCR4 coreceptors on multiple CD4+ cell lines as well as primary human CD4+ T cells and macrophages in vitro yet replicated to very high titers (>80 million RNA copies/ml) in an acutely infected individual.
332 21835785 The ZP6248 T/F virus could also infect cell lines overexpressing the alternative coreceptors GPR15, APJ, and FPRL-1.
333 21835785 These results suggest that the ZP6248 T/F virus established an acute in vivo infection by using coreceptor(s) other than CCR5 or CXCR4 or that the CCR5 coreceptor existed in an unusual conformation in this individual.
334 21835785 The great majority of human immunodeficiency virus type 1 (HIV-1) strains enter CD4+ target cells by interacting with one of two coreceptors, CCR5 or CXCR4.
335 21835785 Here we describe a transmitted/founder (T/F) virus (ZP6248) that was profoundly impaired in its ability to utilize CCR5 and CXCR4 coreceptors on multiple CD4+ cell lines as well as primary human CD4+ T cells and macrophages in vitro yet replicated to very high titers (>80 million RNA copies/ml) in an acutely infected individual.
336 21835785 The ZP6248 T/F virus could also infect cell lines overexpressing the alternative coreceptors GPR15, APJ, and FPRL-1.
337 21835785 These results suggest that the ZP6248 T/F virus established an acute in vivo infection by using coreceptor(s) other than CCR5 or CXCR4 or that the CCR5 coreceptor existed in an unusual conformation in this individual.
338 21835785 The great majority of human immunodeficiency virus type 1 (HIV-1) strains enter CD4+ target cells by interacting with one of two coreceptors, CCR5 or CXCR4.
339 21835785 Here we describe a transmitted/founder (T/F) virus (ZP6248) that was profoundly impaired in its ability to utilize CCR5 and CXCR4 coreceptors on multiple CD4+ cell lines as well as primary human CD4+ T cells and macrophages in vitro yet replicated to very high titers (>80 million RNA copies/ml) in an acutely infected individual.
340 21835785 The ZP6248 T/F virus could also infect cell lines overexpressing the alternative coreceptors GPR15, APJ, and FPRL-1.
341 21835785 These results suggest that the ZP6248 T/F virus established an acute in vivo infection by using coreceptor(s) other than CCR5 or CXCR4 or that the CCR5 coreceptor existed in an unusual conformation in this individual.
342 22002875 A clonal model for human CD8+ regulatory T cells: unrestricted contact-dependent killing of activated CD4+ T cells.
343 22002875 Previous studies in murine systems have demonstrated that CD8(+) Treg cells down-regulate immune responses in vivo through suppressing activated CD4(+) T cells.
344 22002875 Here we describe novel regulatory CD8(+) T-cell clones isolated from healthy human peripheral blood following in vitro stimulation with autologous Epstein-Barr virus (EBV)-specific CD4(+) T cells.
345 22002875 TCR activation of CD4(+) target T cells was required for CD8(+) Treg cells to exert suppressive activity, which was mediated through lysis of CD4(+) targets in a cell contact-dependent manner.
346 22002875 Suppression was independent of Foxp3 expression in CD8(+) Treg cells, HLA compatibility between CD8(+) Treg cells and CD4(+) target cells and antigen-specificity of CD4(+) target T cells.
347 22002875 CD8(+) Treg clones expressed CD3 and a variety of TCR V(β) chains as well as CD56, CD69, CD62L and CD95 but did not express CD16, CD161, CXCR4 and CCR7.
348 22002875 When used together, antibodies specific for CD11a/CD18 and CD8 inhibited suppressive activity of CD8(+) Treg clones.
349 22427637 Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation.
350 22427637 The introduction of Bcl6 expression in primary human CD4 T cells resulted in the regulation of a core set of migration genes that enable trafficking to germinal centers: CXCR4, CXCR5, CCR7, and EBI2.
351 22427637 Bcl6 expression also induced a module of protein expression critical for T-B interactions, including SAP, CD40L, PD-1, ICOS, and CXCL13.
352 22427637 This constitutes direct evidence for Bcl6 control of most of these functions and includes three genes known to be loci of severe human genetic immunodeficiencies (CD40L, SH2D1A, and ICOS).
353 22427637 Introduction of Bcl6 did not alter the expression of IL-21 or IL-4, the primary cytokines of human Tfh cells.
354 22427637 Coexpression of Bcl6 and Maf revealed that Bcl6 and Maf cooperate in the induction of CXCR4, PD-1, and ICOS.
355 22427637 Altogether, these findings reveal that Bcl6 and Maf collaborate to orchestrate a suite of genes that define core characteristics of human Tfh cell biology.
356 22486585 HIV-1 attachment to susceptible cells involves binding of gp120 to CD4 receptor and subsequently to a HIV co-receptor, either CCR5 or CXCR4.
357 22486585 The present review addresses recent advances of CCR5-targeted HSC gene approaches to treat HIV infection, discusses the future prospects and postulates potential strategies in the field.
358 22536342 Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain.
359 23100517 Plasmacytoid dendritic cells (pDCs) play a central role in innate and adaptive immune responses to viral infections, including HIV type 1 (HIV-1). pDCs produce substantial quantities of type I IFN and proinflammatory cytokines upon stimulation via TLRs, specifically TLR7 or TLR9.
360 23100517 Specifically, gp120 inhibited the CpG-induced maturation of pDCs and their expression of TNF-α, IL-6, TLR9, IFN regulatory factor 7, and BAFF.
361 23100517 Receptor-blocking and cross-linking studies showed that these inhibitory effects of gp120 were mediated by interactions with CD4 and mannose-binding C-type lectin receptors, but not with the chemokine receptors CCR5 and CXCR4.
362 23372784 Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies.
363 23372784 Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes.
364 23372784 Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well.
365 23372784 However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor.
366 23685221 Human memory-like NK cells migrating to tuberculous pleural fluid via IP-10/CXCR3 and SDF-1/CXCR4 axis produce IFN-γ in response to Bacille Calmette Guerin.
367 23685221 At present, we found that NK cells from TB pleural fluid cells (PFCs) expressed significantly higher levels of CXCR3 and CXCR4 than NK cells from PBMCs.
368 23685221 Migration assay demonstrated that IP-10 and SDF-1 induced more migration of NK cells from PFCs than PBMCs.
369 23685221 Collectively, our data demonstrated that human Mycobacterium tuberculosis-specific NK cells were migrated into the local site of TB infection mainly via IP-10/CXCR3 and SDF-1/CXCR4 axis, memory-like NK cells might display an important role against M. tuberculosis infection.
370 23685221 Human memory-like NK cells migrating to tuberculous pleural fluid via IP-10/CXCR3 and SDF-1/CXCR4 axis produce IFN-γ in response to Bacille Calmette Guerin.
371 23685221 At present, we found that NK cells from TB pleural fluid cells (PFCs) expressed significantly higher levels of CXCR3 and CXCR4 than NK cells from PBMCs.
372 23685221 Migration assay demonstrated that IP-10 and SDF-1 induced more migration of NK cells from PFCs than PBMCs.
373 23685221 Collectively, our data demonstrated that human Mycobacterium tuberculosis-specific NK cells were migrated into the local site of TB infection mainly via IP-10/CXCR3 and SDF-1/CXCR4 axis, memory-like NK cells might display an important role against M. tuberculosis infection.
374 23685221 Human memory-like NK cells migrating to tuberculous pleural fluid via IP-10/CXCR3 and SDF-1/CXCR4 axis produce IFN-γ in response to Bacille Calmette Guerin.
375 23685221 At present, we found that NK cells from TB pleural fluid cells (PFCs) expressed significantly higher levels of CXCR3 and CXCR4 than NK cells from PBMCs.
376 23685221 Migration assay demonstrated that IP-10 and SDF-1 induced more migration of NK cells from PFCs than PBMCs.
377 23685221 Collectively, our data demonstrated that human Mycobacterium tuberculosis-specific NK cells were migrated into the local site of TB infection mainly via IP-10/CXCR3 and SDF-1/CXCR4 axis, memory-like NK cells might display an important role against M. tuberculosis infection.
378 23757493 Binding the receptors, CD4 and CCR5/CXCR4, triggers Env conformational changes from the metastable unliganded state to the fusion-active state.
379 23764537 Control of humoral immunity and auto-immunity by the CXCR4/CXCL12 axis in lupus patients following influenza vaccine.
380 23992667 The primary determinant of HIV cell tropism is the expression pattern of the primary viral receptor CD4 and co-receptor(s), such as CXCR4 and CCR5.
381 24119449 The HIV-1 co-receptors CCR5 and CXCR4 are genetically stable, but viral proteins may mutate rapidly during the course of infection.
382 24269609 Because chemokines mediate the recruitment of leukocytes through the action of specific chemokine receptors, in the current study, we have studied the transcription of several immune genes in response to a VHSV bath infection in the gills, focusing both on chemokine receptor genes and on genes characteristic of distinct leukocyte populations such as IgM, IgD, IgT, CD4, CD8, perforin and MHC-II.
383 24269609 Our results indicate that despite the low replication level, VHSV provokes an up-regulation of IgM, IgT, CD3 and perforin transcription together with the up-regulation of CCR7, CCR9, CXCR3B and CXCR4 mRNA levels.
384 24269609 Interestingly, MHC-II mRNA was up-regulated and CCR7 was down-modulated in IgM(+) cells from infected gills, whereas perforin, CCR7 and CXCR4 mRNA levels were higher in sorted CD8(+) cells from infected animals.
385 24269609 Because chemokines mediate the recruitment of leukocytes through the action of specific chemokine receptors, in the current study, we have studied the transcription of several immune genes in response to a VHSV bath infection in the gills, focusing both on chemokine receptor genes and on genes characteristic of distinct leukocyte populations such as IgM, IgD, IgT, CD4, CD8, perforin and MHC-II.
386 24269609 Our results indicate that despite the low replication level, VHSV provokes an up-regulation of IgM, IgT, CD3 and perforin transcription together with the up-regulation of CCR7, CCR9, CXCR3B and CXCR4 mRNA levels.
387 24269609 Interestingly, MHC-II mRNA was up-regulated and CCR7 was down-modulated in IgM(+) cells from infected gills, whereas perforin, CCR7 and CXCR4 mRNA levels were higher in sorted CD8(+) cells from infected animals.
388 24312168 The current assay of choice uses a non-lymphoid cell line (TZM-bl) that may lack sensitivity owing to over expression of CD4 and CCR5.
389 24312168 We used transfection of a human CD4+/CXCR4+/α4β7+ T-lymphoblastoid cell line (A3.01) with a CMV IE promoter-driven CCR5neo vector to stably express CCR5.
390 24348253 Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.
391 24348253 Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro.
392 24348253 Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers.
393 24348253 CD69 expression was increased in semen T cells by SIV infection, at all stages of infection.
394 24348253 Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1.
395 24348253 Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages).
396 24501341 Our data show that (i) there was an antibody response to LCR1 in each individual with a recent history of visceral leishmaniasis studied, (ii) there was neither a proliferative response nor production of gamma interferon (IFN-γ) or interleukin 10 in response to LCR1 by mononuclear cells from individuals who had recovered from visceral leishmaniasis, and (iii) individuals who have recovered from visceral leishmaniasis show ongoing immune responses long after recovery from the disease.
397 24632660 CXCR4 activation by the specific ligand C-X-C motif chemokine 12 (CXCL12) induces several intracellular signaling pathways that have been selectively related to malignancy depending on the tissue or cell type.
398 24814239 Unlike humans, macaque mucosal memory B-cells lacked CD27 expression; only two sub-populations were present: naïve (CD21(+)CD27(-)) and tissue-like (CD21(-)CD27(-)) memory.
399 24814239 The homing markers CXCR4, CCR6, CCR9 and α4β7 were differentially expressed between naïve and tissue-like memory B-cells.
400 24814239 Mucosal plasmablasts were identified as CD19(+)CD20(+/-)HLA-DR(+)Ki-67(+)IRF4(+)CD138(+/-) and mucosal plasma cells as CD19(+)CD20(-)HLA-DR(-)Ki-67(-)IRF4(+)CD138(+).
401 24814239 Both populations were CD39(+/-)CD27(-).
402 24821968 Elmo1 and Elmo2 are highly homologous cytoplasmic adaptor proteins that interact with Dock family guanine nucleotide exchange factors to promote activation of the small GTPase Rac.
403 24821968 In T lymphocytes, Dock2 is essential for CCR7- and CXCR4-dependent Rac activation and chemotaxis, but the role of Elmo proteins in regulating Dock2 function in primary T cells is not known.
404 24821968 In this article, we show that endogenous Elmo1, but not Elmo2, interacts constitutively with Dock2 in mouse and human primary T cells.
405 24821968 CD4(+) T cells from Elmo1(-/-) mice were profoundly impaired in polarization, Rac activation, and chemotaxis in response to CCR7 and CXCR4 stimulation.
406 24821968 Transfection of full-length Elmo1, but not Elmo2 or a Dock2-binding mutant of Elmo1, rescued defective migration of Elmo1(-/-) T cells.
407 24821968 Interestingly, Dock2 protein levels were reduced by 4-fold in Elmo1(-/-) lymphocytes despite normal levels of Dock2 mRNA.
408 24821968 Dock2 polyubiquitination was increased in Elmo1(-/-) T cells, and treatment with proteasome inhibitors partially restored Dock2 levels in Elmo1(-/-) T cells.
409 24821968 Finally, we show that Dock2 is directly ubiquitinated in CD4(+) T cells and that Elmo1 expression in heterologous cells inhibits ubiquitination of Dock2.
410 24821968 Taken together, these findings reveal a previously unknown, nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes.
411 24821968 This work provides valuable insights into the molecular regulation of Dock2 by Elmo1 that can be used to design improved inhibitors that target the Elmo-Dock-Rac signaling complex.
412 24821968 Elmo1 and Elmo2 are highly homologous cytoplasmic adaptor proteins that interact with Dock family guanine nucleotide exchange factors to promote activation of the small GTPase Rac.
413 24821968 In T lymphocytes, Dock2 is essential for CCR7- and CXCR4-dependent Rac activation and chemotaxis, but the role of Elmo proteins in regulating Dock2 function in primary T cells is not known.
414 24821968 In this article, we show that endogenous Elmo1, but not Elmo2, interacts constitutively with Dock2 in mouse and human primary T cells.
415 24821968 CD4(+) T cells from Elmo1(-/-) mice were profoundly impaired in polarization, Rac activation, and chemotaxis in response to CCR7 and CXCR4 stimulation.
416 24821968 Transfection of full-length Elmo1, but not Elmo2 or a Dock2-binding mutant of Elmo1, rescued defective migration of Elmo1(-/-) T cells.
417 24821968 Interestingly, Dock2 protein levels were reduced by 4-fold in Elmo1(-/-) lymphocytes despite normal levels of Dock2 mRNA.
418 24821968 Dock2 polyubiquitination was increased in Elmo1(-/-) T cells, and treatment with proteasome inhibitors partially restored Dock2 levels in Elmo1(-/-) T cells.
419 24821968 Finally, we show that Dock2 is directly ubiquitinated in CD4(+) T cells and that Elmo1 expression in heterologous cells inhibits ubiquitination of Dock2.
420 24821968 Taken together, these findings reveal a previously unknown, nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes.
421 24821968 This work provides valuable insights into the molecular regulation of Dock2 by Elmo1 that can be used to design improved inhibitors that target the Elmo-Dock-Rac signaling complex.
422 24897520 However, we recently identified a transmitted/founder (T/F) virus (ZP6248) that efficiently used an alternative coreceptor GPR15, rather than commonly used CXCR4 and CCR5, to establish clinical infection.
423 24897520 These results demonstrated that amino acids in ZP6248 V3 might form a unique conformation that was critical for the interaction with GPR15 while the amino acids at position 314 in the V3 crown of ZP6248 played a key role in interaction with both CCR5 and GPR15.
424 25070183 Stromal-derived factor 1α (SDF‑1α, also known as CXCL12) is a chemokine that exerts its effects through the G-protein coupled receptors, C-X-C chemokine receptor type 4 (CXCR4) and 7 (CXCR7).
425 25070183 There is marked evidence that the SDF-1/CXCR4 axis is involved in the pathogenesis of leukemia and therapies that target this axis are under development.
426 25070183 Stromal-derived factor 1α (SDF‑1α, also known as CXCL12) is a chemokine that exerts its effects through the G-protein coupled receptors, C-X-C chemokine receptor type 4 (CXCR4) and 7 (CXCR7).
427 25070183 There is marked evidence that the SDF-1/CXCR4 axis is involved in the pathogenesis of leukemia and therapies that target this axis are under development.
428 25191323 Furthermore, using high-color flow-cytometry, on day 7 after immunization, we observed the appearance of conventional PB (CPB, CD19(dim) CD20(-) CD27(+high) CD38(+high) CD3(-)), as well as a PB population that did not express CD27 (CD27(-) PB; pre-plasmablasts).
429 25191323 The pattern of individual or simultaneous expression of homing markers (integrin α4β7, CD62L, CXCR3, and CXCR4) suggested that CPB cells homed preferentially to the inflamed gut mucosa.
430 25224013 Cellular and biochemical assays were used to elucidate the antiviral mechanisms of action of PDB oligomers against both lab-adapted and primary CCR5- and CXCR4-utilizing HIV-1 strains, including a multidrug-resistant isolate.
431 25795219 The CXC chemokine receptor 4 (CXCR4) is the cognate receptor of the CXC chemokine ligand 12 (CXCL12) and plays a pivotal role under immune-pathophysiological conditions.
432 26039883 The 'improved' maturation cytokine cocktail DCs showed a higher levels surface markers expression (CD80, CD83, CD86 and HLA-DR), the chemokine receptors CXCR4 and CCR7 and chemokine CCL19, CCL21 and CXCL21, whereas CCR5 expression was reduced.
433 26229980 Previous studies, using phorbol-myristate-acetate (PMA) as a differentiating agent, have suggested that the CD34+/CD38+ TF-1 cell line may be used as one model to study the differentiation processes of HPCs.
434 26229980 The conditioned medium (CM) from this bone marrow-derived cell population is enriched with respect to numerous cytokines and induces differentiation and activation of TF-1 cells, as indicated by changes in the expression of CD34, CD38, and CD69 cell surface molecules.
435 26229980 Furthermore, treatment with CM was also shown to induce the expression of CCR5 and CXCR4, while maintaining the expression of CD4, which was ultimately correlated with increased susceptibility to HIV-1.
436 26259811 An HIV-1 infection in a host cell occurs through an ordered process that involves HIV-1 attachment to the host's cellular CD4 receptor, co-receptor binding to CCR5 or CXCR4, and the subsequent fusion with the cellular membrane.
437 26339033 Experiments with granulocyte-specific CXCL12 conditionally depleted mice and a CXCR4 antagonist revealed that CXCL12 derived from neutrophil trails is critical for virus-specific CD8(+) T cell recruitment and effector functions.
438 26435001 We also observed that inhibition of CXCL12 binding to its receptors CXCR4 and CXCR7 by chalcone 4 blocked BPAF-induced cell growth.