hiv receptors


Summary: Cellular receptors that bind the human immunodeficiency virus that causes AIDS. Included are CD4 ANTIGENS, found on T4 lymphocytes, and monocytes/macrophages, which bind to the HIV ENVELOPE PROTEIN GP120.

Top Publications

  1. Troyer R, Collins K, Abraha A, Fraundorf E, Moore D, Krizan R, et al. Changes in human immunodeficiency virus type 1 fitness and genetic diversity during disease progression. J Virol. 2005;79:9006-18 pubmed
    ..These data provide in vivo evidence that increasing HIV-1 replication efficiency may be related to a concomitant increase in HIV-1 diversity, which in turn may be a determining factor in disease progression. ..
  2. Genebat M, Ruiz Mateos E, Leon J, Gonzalez Serna A, Pulido I, Rivas I, et al. Correlation between the Trofile test and virological response to a short-term maraviroc exposure in HIV-infected patients. J Antimicrob Chemother. 2009;64:845-9 pubmed publisher
    ..This clinical approach shows high concordance with Trofile, and could allow patients with non-reportable results by Trofile to benefit from maraviroc therapy. ..
  3. Rose J, Rhea A, Weber J, Quinones Mateu M. Current tests to evaluate HIV-1 coreceptor tropism. Curr Opin HIV AIDS. 2009;4:136-42 pubmed publisher
    ..Further studies, aimed to the development of novel methodologies, are essential for the success of this new class of drugs. ..
  4. Boisvert S, Marchand M, Laviolette F, Corbeil J. HIV-1 coreceptor usage prediction without multiple alignments: an application of string kernels. Retrovirology. 2008;5:110 pubmed publisher
    ..We also show how to extract the most relevant features for HIV-1 coreceptor usage. The SVM with the distant segments kernel is currently the best method described. ..
  5. Lamers S, Salemi M, McGrath M, Fogel G. Prediction of R5, X4, and R5X4 HIV-1 coreceptor usage with evolved neural networks. IEEE/ACM Trans Comput Biol Bioinform. 2008;5:291-300 pubmed publisher
    ..We demonstrate the use of artificial neural networks trained via evolutionary computation to predict viral co-receptor usage. The results indicate identification of R5X4 viruses with predictive accuracy of 75.5%. ..
  6. Mild M, Esbjörnsson J, Fenyo E, Medstrand P. Frequent intrapatient recombination between human immunodeficiency virus type 1 R5 and X4 envelopes: implications for coreceptor switch. J Virol. 2007;81:3369-76 pubmed
    ..In conclusion, intrapatient recombination between viruses with distinct coreceptor usage may contribute to the emergence of X4 viruses in later stages of infection. ..
  7. Rullas J, Bermejo M, Garcia Perez J, Beltán M, González N, Hezareh M, et al. Prostratin induces HIV activation and downregulates HIV receptors in peripheral blood lymphocytes. Antivir Ther. 2004;9:545-54 pubmed
    ..did not inhibit infection with a pseudotyped viral clone that enters into the cells independently of HIV receptors. These results help to explain the paradoxical effects of prostratin...
  8. Glushakova S, Yi Y, Grivel J, Singh A, Schols D, De Clercq E, et al. Preferential coreceptor utilization and cytopathicity by dual-tropic HIV-1 in human lymphoid tissue ex vivo. J Clin Invest. 1999;104:R7-R11 pubmed
  9. Kwong P, Doyle M, Casper D, Cicala C, Leavitt S, Majeed S, et al. HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Nature. 2002;420:678-82 pubmed
    ..Because this solution is available for cell-surface receptors but not for most antibodies, conformational masking enables HIV-1 to maintain receptor binding and simultaneously to resist neutralization. ..

More Information


  1. Zhang Y, Lou B, Lal R, Gettie A, Marx P, Moore J. Use of inhibitors to evaluate coreceptor usage by simian and simian/human immunodeficiency viruses and human immunodeficiency virus type 2 in primary cells. J Virol. 2000;74:6893-910 pubmed
    ..The replication in human PBMC of SIV(rcm) (from a red-capped mangabey), a virus which uses CCR2 but not CCR5 for entry, was blocked by TAK-779, suggesting that CCR2 is indeed the paramount coreceptor for this virus in primary cells. ..
  2. Bobardt M, Saphire A, Hung H, Yu X, Van der Schueren B, Zhang Z, et al. Syndecan captures, protects, and transmits HIV to T lymphocytes. Immunity. 2003;18:27-39 pubmed
    ..Moreover, we obtain evidence suggesting that the vast syndecan-rich endothelial lining of the vasculature can provide a microenvironment which boosts HIV replication in T cells. ..
  3. Ogert R, Ba L, Hou Y, Buontempo C, Qiu P, Duca J, et al. Structure-function analysis of human immunodeficiency virus type 1 gp120 amino acid mutations associated with resistance to the CCR5 coreceptor antagonist vicriviroc. J Virol. 2009;83:12151-63 pubmed publisher
    ..The cumulative results of this study suggest that as the RU570 VCV-resistant virus adapted to use the drug-bound receptor, it also developed an increased reliance on the N terminus of CCR5. ..
  4. Biscone M, Miamidian J, Muchiri J, Baik S, Lee F, Doms R, et al. Functional impact of HIV coreceptor-binding site mutations. Virology. 2006;351:226-36 pubmed
    ..Thus, mutations that reduce coreceptor binding and enhance susceptibility to coreceptor inhibitors can affect fusion and enfuvirtide susceptibility in an Env context-dependent manner. ..
  5. Hu Q, Frank I, Williams V, Santos J, Watts P, Griffin G, et al. Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue. J Exp Med. 2004;199:1065-75 pubmed
    ..Our identification of the predominant receptors involved in HIV-1 infection and dissemination within human cervical tissue highlight important targets for microbicide development. ..
  6. Meng G, Wei X, Wu X, Sellers M, Decker J, Moldoveanu Z, et al. Primary intestinal epithelial cells selectively transfer R5 HIV-1 to CCR5+ cells. Nat Med. 2002;8:150-6 pubmed
    ..Our finding that CCR5+ intestinal epithelial cells select and transfer exclusively R5 viruses indicates a mechanism for the selective transmission of R5 HIV-1 in primary infection acquired through the upper gastrointestinal tract. ..
  7. Briggs D, Tuttle D, Sleasman J, Goodenow M. Envelope V3 amino acid sequence predicts HIV-1 phenotype (co-receptor usage and tropism for macrophages). AIDS. 2000;14:2937-9 pubmed
  8. Pollakis G, Kang S, Kliphuis A, Chalaby M, Goudsmit J, Paxton W. N-linked glycosylation of the HIV type-1 gp120 envelope glycoprotein as a major determinant of CCR5 and CXCR4 coreceptor utilization. J Biol Chem. 2001;276:13433-41 pubmed
    ..These results demonstrate that the N-linked glycosylation pattern of the HIV-1 envelope can strongly influence viral coreceptor utilization and the R5 to X4 switch. ..
  9. Pantophlet R, Burton D. GP120: target for neutralizing HIV-1 antibodies. Annu Rev Immunol. 2006;24:739-69 pubmed
    ..These include (a) the construction of mimics of the viral envelope spike and (b) the design of antigens specifically tailored to induce broadly neutralizing antibodies. ..
  10. Tchou I, Misery L, Sabido O, Dezutter Dambuyant C, Bourlet T, Moja P, et al. Functional HIV CXCR4 coreceptor on human epithelial Langerhans cells and infection by HIV strain X4. J Leukoc Biol. 2001;70:313-21 pubmed
    ..These data demonstrated that CXCR4 is present on the surface of Langerhans cells freshly isolated from human skin epidermis and that this expression is functional. ..
  11. Shimizu N, Soda Y, Kanbe K, Liu H, Mukai R, Kitamura T, et al. A putative G protein-coupled receptor, RDC1, is a novel coreceptor for human and simian immunodeficiency viruses. J Virol. 2000;74:619-26 pubmed
    ..The cells also acquired a low susceptibility to the HIV-1 variants. These findings indicate that RDC1 is a novel coreceptor for several HIV-1, HIV-2, and SIV strains which infect brain-derived cells. ..
  12. Geijtenbeek T, Torensma R, van Vliet S, van Duijnhoven G, Adema G, van Kooyk Y, et al. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell. 2000;100:575-85 pubmed
    ..Since antibodies against DC-SIGN inhibit DC-induced proliferation of resting T cells, our findings predict that DC-SIGN enables T cell receptor engagement by stabilization of the DC-T cell contact zone. ..
  13. Casper C, Naver L, Clevestig P, Belfrage E, Leitner T, Albert J, et al. Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes. AIDS Res Hum Retroviruses. 2002;18:343-52 pubmed
    ..Thus CXCR4-using virus may emerge as a possible consequence of immune deficiency. The results provide new insights into AIDS development in children. ..
  14. Jotwani R, Muthukuru M, Cutler C. Increase in HIV receptors/co-receptors/alpha-defensins in inflamed human gingiva. J Dent Res. 2004;83:371-7 pubmed
    ..Thus, low expression of HIV-1 co-receptors in health and high expression of alpha-defensin during CP may comprise endogenous factors that provide protection from oral HIV-1 infection. ..
  15. Jensen M, van t Wout A. Predicting HIV-1 coreceptor usage with sequence analysis. AIDS Rev. 2003;5:104-12 pubmed
    ..Further development of these methods, by extending analysis to regions outside the V3 loop and to clades beyond subtype B, will extend our understanding of HIV-1 pathogenesis and inform treatment strategies. ..
  16. Cilliers T, Nhlapo J, Coetzer M, Orlovic D, Ketas T, Olson W, et al. The CCR5 and CXCR4 coreceptors are both used by human immunodeficiency virus type 1 primary isolates from subtype C. J Virol. 2003;77:4449-56 pubmed
    ..These observations are relevant to understanding the rapid spread of HIV-1 subtype C in the developing world and to the design of intervention and treatment strategies. ..
  17. Devesa F, Chams V, Dinadayala P, Stella A, Ragas A, Auboiroux H, et al. Functional reconstitution of the HIV receptors CCR5 and CD4 in liposomes. Eur J Biochem. 2002;269:5163-74 pubmed
    ..Thus, functional coreconstitution of two widely different proteins can be achieved by this method, suggesting that it might be useful for other proteins. ..
  18. Zhang H, Hoffmann F, He J, He X, Kankasa C, West J, et al. Characterization of HIV-1 subtype C envelope glycoproteins from perinatally infected children with different courses of disease. Retrovirology. 2006;3:73 pubmed
  19. Stantchev T, Broder C. Human immunodeficiency virus type-1 and chemokines: beyond competition for common cellular receptors. Cytokine Growth Factor Rev. 2001;12:219-43 pubmed
  20. Fotopoulos G, Harari A, Michetti P, Trono D, Pantaleo G, Kraehenbuhl J. Transepithelial transport of HIV-1 by M cells is receptor-mediated. Proc Natl Acad Sci U S A. 2002;99:9410-4 pubmed
    ..The follicle-associated epithelium covering human gut lymphoid follicles expresses CCR5, but not CXCR4, and lactosyl cerebroside, suggesting that HIV-1 infection may occur through M cells and enterocytes at these sites. ..
  21. Aasa Chapman M, Seymour C, Williams I, McKnight A. Novel envelope determinants for CCR3 use by human immunodeficiency virus. J Virol. 2006;80:10884-9 pubmed
    ..The other two, R440 and N448 in conserved region 4, are proximal to but distinct from residues already identified as being important for CCR5 binding. ..
  22. Hoffmann C. The epidemiology of HIV coreceptor tropism. Eur J Med Res. 2007;12:385-90 pubmed
    ..This review will focus on current knowledge of the epidemiology of HIV coreceptor tropism. ..
  23. Morris L, Cilliers T, Bredell H, Phoswa M, Martin D. CCR5 is the major coreceptor used by HIV-1 subtype C isolates from patients with active tuberculosis. AIDS Res Hum Retroviruses. 2001;17:697-701 pubmed
    ..It is possible that activation of monocytes and macrophages during TB infection results in the expansion of macrophage-tropic isolates that preferentially use CCR5. ..
  24. Li B, Wetzel M, Mikovits J, Henderson E, Rogers T, Gong W, et al. The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1. Blood. 2001;97:2941-7 pubmed
    ..Blood. 2001;97:2941-2947) ..
  25. McDonald D, Wu L, Bohks S, Kewalramani V, Unutmaz D, Hope T. Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science. 2003;300:1295-7 pubmed
    ..of conjugates between MDDCs and T cells revealed that, in the absence of antigen-specific signaling, the HIV receptors CD4, CCR5, and CXCR4 on the T cell were recruited to the interface while the MDDCs concentrated HIV to the ..
  26. Binninger Schinzel D, Muller D, Wolf T, Krause B, Meye B, Winskowsky G, et al. Characterization of a chemokine receptor CCR5-negative T cell line and its use in determining human immunodeficiency virus type 1 phenotype. J Med Virol. 2008;80:192-200 pubmed
  27. Hartley O, Klasse P, Sattentau Q, Moore J. V3: HIV's switch-hitter. AIDS Res Hum Retroviruses. 2005;21:171-89 pubmed
    ..Here, we review recent advances in the understanding of V3 as a determinant of viral tropism, and discuss how this new knowledge may inform the development of HIV-1 drugs and vaccines. ..
  28. Geijtenbeek T, Kwon D, Torensma R, van Vliet S, van Duijnhoven G, Middel J, et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 2000;100:587-97 pubmed
    ..We propose that DC-SIGN efficiently captures HIV-1 in the periphery and facilitates its transport to secondary lymphoid organs rich in T cells, to enhance infection in trans of these target cells. ..
  29. Xu S, Huang X, Xu H, Zhang C. Improved prediction of coreceptor usage and phenotype of HIV-1 based on combined features of V3 loop sequence using random forest. J Microbiol. 2007;45:441-6 pubmed
    ..Among these features, V3 polarity and four V3 sites (22, 12, 18 and 13) are first reported to have high contribution to HIV-1 biological phenotype prediction. ..
  30. Turville S, Cameron P, Handley A, Lin G, Pohlmann S, Doms R, et al. Diversity of receptors binding HIV on dendritic cell subsets. Nat Immunol. 2002;3:975-83 pubmed
    ..The diversity of CLRs able to bind HIV-1 in skin DCs may reflect their ability to bind a range of microbial glycoproteins. ..
  31. Bandivdekar A, Velhal S, Raghavan V. Identification of CD4-independent HIV receptors on spermatozoa. Am J Reprod Immunol. 2003;50:322-7 pubmed
    ..Present communication describes the identification of HIV receptors on the spermatozoa...
  32. Gorry P, Churchill M, Crowe S, Cunningham A, Gabuzda D. Pathogenesis of macrophage tropic HIV-1. Curr HIV Res. 2005;3:53-60 pubmed
    ..These variants are likely to impact HIV-1 disease progression, particularly in patients who persistently harbor only R5 viral strains. ..
  33. Pastore C, Nedellec R, Ramos A, Pontow S, Ratner L, Mosier D. Human immunodeficiency virus type 1 coreceptor switching: V1/V2 gain-of-fitness mutations compensate for V3 loss-of-fitness mutations. J Virol. 2006;80:750-8 pubmed
    ..HIV-1 envelope sequence evolution from CCR5 to CXCR4 use is constrained by relatively frequent lethal mutations, deep fitness valleys, and requirements to make the right amino acid substitution in the right place at the right time. ..
  34. Kumar R, Maher D, Herzberg M, Southern P. Expression of HIV receptors, alternate receptors and co-receptors on tonsillar epithelium: implications for HIV binding and primary oral infection. Virol J. 2006;3:25 pubmed human mucosal surfaces, we have examined the distribution of the primary HIV receptor CD4, the alternate HIV receptors heparan sulfate proteoglycan (HS) and galactosyl ceramide (GalCer) and the co-receptors CXCR4 and CCR5 in ..
  35. Clapham P, McKnight A. Cell surface receptors, virus entry and tropism of primate lentiviruses. J Gen Virol. 2002;83:1809-29 pubmed
    ..Other cell surface receptors also interact with gp120 and aid attachment of virus particles. This review describes these receptors, their roles in HIV entry and their influence on cell tropism. ..
  36. Prosperi M, Fanti I, Ulivi G, Micarelli A, De Luca A, Zazzi M. Robust supervised and unsupervised statistical learning for HIV type 1 coreceptor usage analysis. AIDS Res Hum Retroviruses. 2009;25:305-14 pubmed publisher
    ..A high-performing, compact, and interpretable logistic regression model was derived to infer HIV-1 coreceptor tropism for a given patient [accuracy = 92.76 (SD 3.07); AUC = 0.93 (SD 0.04)]. ..
  37. Moore J, Rahemtulla F, Kent L, Hall S, Ikizler M, Wright P, et al. Oral epithelial cells are susceptible to cell-free and cell-associated HIV-1 infection in vitro. Virology. 2003;313:343-53 pubmed
    ..These data have potential implications in the transmission of HIV-1 in the oral cavity. ..
  38. Gray L, Sterjovski J, Churchill M, Ellery P, Nasr N, Lewin S, et al. Uncoupling coreceptor usage of human immunodeficiency virus type 1 (HIV-1) from macrophage tropism reveals biological properties of CCR5-restricted HIV-1 isolates from patients with acquired immunodeficiency syndrome. Virology. 2005;337:384-98 pubmed
    ..Thus, reduced CD4/CCR5 dependence is a phenotype of R5 HIV-1 associated with M-tropism and late stage infection, which may affect the efficacy of HIV-1 entry inhibitors. ..
  39. Turville S, Arthos J, Donald K, Lynch G, Naif H, Clark G, et al. HIV gp120 receptors on human dendritic cells. Blood. 2001;98:2482-8 pubmed
    ..In view of these marked differences between MDDCs and blood DCs, HIV capture by DCs and transfer mechanisms to T cells as well as potential antigenic processing pathways will need to be determined for each DC phenotype. ..
  40. Gorry P, Dunfee R, Mefford M, Kunstman K, Morgan T, Moore J, et al. Changes in the V3 region of gp120 contribute to unusually broad coreceptor usage of an HIV-1 isolate from a CCR5 Delta32 heterozygote. Virology. 2007;362:163-78 pubmed
  41. Lengauer T, Sander O, Sierra S, Thielen A, Kaiser R. Bioinformatics prediction of HIV coreceptor usage. Nat Biotechnol. 2007;25:1407-10 pubmed
  42. Saphire A, Bobardt M, Zhang Z, David G, Gallay P. Syndecans serve as attachment receptors for human immunodeficiency virus type 1 on macrophages. J Virol. 2001;75:9187-200 pubmed
    ..Most importantly, we demonstrate that a single family of HSPGs, the syndecans, efficiently mediates HIV-1 attachment and represents an abundant class of attachment receptors on macrophages. ..
  43. Chen Z, Zhou P, Ho D, Landau N, Marx P. Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry. J Virol. 1997;71:2705-14 pubmed
    ..These findings indicated that, in addition to CCR5, SIV can use one or more unknown coreceptors that are expressed on human PBMCs and CEMx174 cells. ..
  44. Wu L, Gerard N, Wyatt R, Choe H, Parolin C, Ruffing N, et al. CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature. 1996;384:179-83 pubmed
    ..These results suggest that HIV-1 attachment to CD4 creates a high-affinity binding site for CCR-5, leading to membrane fusion and virus entry. ..
  45. Shimizu N, Soda Y, Kanbe K, Liu H, Jinno A, Kitamura T, et al. An orphan G protein-coupled receptor, GPR1, acts as a coreceptor to allow replication of human immunodeficiency virus types 1 and 2 in brain-derived cells. J Virol. 1999;73:5231-9 pubmed
    ..These results indicate that GPR1 functions as a coreceptor for the HIV-1 variants and mutants and for the HIV-2ROD strain in vitro. ..
  46. Berger E, Murphy P, Farber J. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol. 1999;17:657-700 pubmed
    ..Beyond providing new perspectives on fundamental aspects of HIV-1 transmission and pathogenesis, the coreceptors suggest new avenues for developing novel therapeutic and preventative strategies to combat the AIDS epidemic. ..
  47. Farzan M, Choe H, Martin K, Marcon L, Hofmann W, Karlsson G, et al. Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection. J Exp Med. 1997;186:405-11 pubmed
    ..These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis. ..
  48. Delezay O, Koch N, Yahi N, Hammache D, Tourres C, Tamalet C, et al. Co-expression of CXCR4/fusin and galactosylceramide in the human intestinal epithelial cell line HT-29. AIDS. 1997;11:1311-8 pubmed
    ..These data raise the possibility that CXCR4/fusin may function as a coreceptor for HIV-1 entry into CD4-/GalCer+ intestinal epithelial cells. ..
  49. Liao F, Alkhatib G, Peden K, Sharma G, Berger E, Farber J. STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1. J Exp Med. 1997;185:2015-23 pubmed
    ..Based on the pattern of tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function with Envs of differing tropisms, STRL33 may play a role in the establishment and/or progression of HIV-1 infection. ..
  50. Samson M, Edinger A, Stordeur P, Rucker J, Verhasselt V, Sharron M, et al. ChemR23, a putative chemoattractant receptor, is expressed in monocyte-derived dendritic cells and macrophages and is a coreceptor for SIV and some primary HIV-1 strains. Eur J Immunol. 1998;28:1689-700 pubmed
    ..Future work will be required to identify the ligand(s) of this new G protein-coupled receptor and to define its precise role in the physiology of dendritic cells and macrophages. ..
  51. He J, Chen Y, Farzan M, Choe H, Ohagen A, Gartner S, et al. CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature. 1997;385:645-9 pubmed
    ..The CCR3 ligand, eotaxin, and an anti-CCR3 antibody inhibited HIV-1 infection of microglia, as did MIP-1beta, which is a CCR5 ligand. Our results suggest that both CCR3 and CCR5 promote efficient infection of the CNS by HIV-1. ..
  52. Bleul C, Farzan M, Choe H, Parolin C, Clark Lewis I, Sodroski J, et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature. 1996;382:829-33 pubmed
  53. Oberlin E, Amara A, Bachelerie F, Bessia C, Virelizier J, Arenzana Seisdedos F, et al. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature. 1996;382:833-5 pubmed