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HIV Entry and Tropism

When One Receptor Is Not Enough

  • Chapter
Mechanisms of Lymphocyte Activation and Immune Regulation VII

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 452))

Abstract

Specific chemokine receptors have recently been identified as the elusive“coreceptors” mediating HIV entry and tropism for different target cells (reviewed in1). Beyond the obvious implications for understanding the entry mechanism, these discoveries have dramatically influenced perspectives on the broader issues of HIV transmission, pathogenesis, and therapy. This chapter summarizes the discovery of the coreceptors, the expansion of the coreceptor repertoire, and the ways in which these findings have illuminated our understanding of the molecular mechanisms underlying HIV fusion and tropism.

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References

  1. Berger EA: HIV entry and tropism: the chemokine receptor connection. AIDS 11, Suppl. A: S3–S16, 1997.

    PubMed  Google Scholar 

  2. Miedema F, Meyaard L, Koot M, Klein MR, Roos MTL, Groenink M, Fouchier RAM, Van’t Wout AB, Tersmette M, Schellekens PTA, Schuitemaker H: Changing virus-host interactions in the course of HIV-1 infection. Immunol Rev 140: 35–72, 1994.

    Article  PubMed  CAS  Google Scholar 

  3. Broder CC, Berger EA: Fusogenic selectivity of the envelope glycoprotein is a major determinant of human immunodeficiency virus type 1 tropism for CD4+ T-cell lines vs. primary macrophages. Proc Natl Acad Sci USA 92: 9004–9008, 1995.

    Article  CAS  Google Scholar 

  4. Alkhatib G, Broder CC, Berger EA: Cell type-specific fusion cofactors determine human immunodeficiency virus type 1 tropism for T-cell lines versus primary macrophages. J Virol 70: 5487–5494, 1996.

    PubMed  CAS  Google Scholar 

  5. Nussbaum O, Broder CC, Berger EA: Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation. J Virol 68: 5411–5422, 1994.

    PubMed  CAS  Google Scholar 

  6. Feng Y, Broder CC, Kennedy PE, Berger EA: HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272: 872–877, 1996.

    Article  PubMed  CAS  Google Scholar 

  7. Bleul CC, Farzan M, Choe H, Parolin C, Clark-Lewis I, Sodroski J, Springer TA: The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/ fusin and blocks HIV-1 entry. Nature 382: 829–833, 1996.

    Article  PubMed  CAS  Google Scholar 

  8. Oberlin E, Amara A, Bachelerie F, Bessia C, Virelizier JL, Arenzana-Seisdedos F, Schwartz O, Heard JM, Clark-Lewis I, Legier DF, Loetscher M, Baggiolini M, Moser B: The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 382: 833–835, 1996.

    Article  PubMed  CAS  Google Scholar 

  9. Cocchi F, DeVico AL, Garzinodemo A, Arya SK, Gallo RC, Lusso P: Identification of RANTES, MIP-1α, and MIP-1β as the major HIV-suppressive factors produced by CD8+ T cells. Science 270: 1811–1815, 1995.

    Article  PubMed  CAS  Google Scholar 

  10. Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M: Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 35: 3362–3367, 1996.

    Article  PubMed  CAS  Google Scholar 

  11. Combadiere C, Ahuja SK, Tiffany HL, Murphy PM: Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MlP-1α, MIP-1α, and RANTES. J Leukocyte Biol 60: 147–152, 1996.

    PubMed  CAS  Google Scholar 

  12. Deng HK, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR: Identification of a major co-receptor for primary isolates of HIV-1. Nature 381: 661–666, 1996.

    Article  PubMed  CAS  Google Scholar 

  13. Dragic T, Litwin V, Allaway GP, Martin SR, Huang YX, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, Paxton WA: HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381:667–673, 1996.

    Article  PubMed  CAS  Google Scholar 

  14. Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA: CC CKR5: A RANTES, MlP-1α, MIP-1β receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272: 1955–1958, 1996.

    Article  PubMed  CAS  Google Scholar 

  15. Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, Larosa G, Newman W, Gerard N, Gerard C, Sodroski J: The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85: 1135–1148, 1996.

    Article  PubMed  CAS  Google Scholar 

  16. Doranz BJ, Rucker J, Yi YJ, Smyth RJ, Samson M, Peiper SC, Parmentier M, Collman RG, Doms RW: A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 85: 1149–1158, 1996.

    Article  PubMed  CAS  Google Scholar 

  17. Rucker J, Edinger AL, Sharron M, Samson M, Lee B, Berson JF, Yi Y, Margulies B, Collman RG, Doranz BJ, Parmentier M, Doms RW: Utilization of chemokine receptors, orphan receptors, and herpesvirus-en-coded receptors by diverse human and simian immunodeficiency viruses. J Virol 71: 8999–9007, 1997.

    PubMed  CAS  Google Scholar 

  18. Horuk R, Hesselgesser J, Zhou Y, Faulds D, Halks-Miller M, Harvey S, Taub D, Samson M, Parmentier M, Rucker J, Doranz BJ, Doms RW: The CC chemokine 1–309 inhibits CCR8-dependent infection by diverse HIV-1 strains. J Biol Chem 273: 386–391, 1998.

    Article  PubMed  CAS  Google Scholar 

  19. Bazan HA, Alkhatib G, Tiffany HL, Bonner TI, Murphy PM, Berger EA: HIV-1 coreceptor activity of CCR8, a receptor for the CC chemokine I-309. submitted.

    Google Scholar 

  20. Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM: Identification of CX3CR1: a chemotactic receptor for fractalkine and a coreceptor for HIV-1. submitted.

    Google Scholar 

  21. Liao F, Alkhatib G, Peden KWC, Sharma G, Berger EA, Färber JM: STRL33, a novel chemokine receptorlike protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1. J Exp Med 185: 2015–2023, 1997.

    Article  PubMed  CAS  Google Scholar 

  22. Alkhatib G, Liao F, Berger EA, Farber JM, Peden KWC: A new SIV co-receptor, STRL33. Nature 388: 238, 1997.

    Article  PubMed  CAS  Google Scholar 

  23. Deng H, Unutmaz D, Kewalramani VN, Littman DR: Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature 388: 296–300, 1997.

    Article  PubMed  CAS  Google Scholar 

  24. Farzan M, Choe H, Martin K, Marcon L, Hofmann W, Karlsson G, Sun Y, Barrett P, Marchand N, Sullivan N, Gerard N, Gerard C, Sodroski J: Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection. J Exp Med 186: 405–411, 1997.

    Article  PubMed  CAS  Google Scholar 

  25. Zhang LQ, Huang YX, He T, Cao YZ, Ho DD: HIV-1 subtype and second-receptor use. Nature 383: 768, 1996.

    Article  PubMed  CAS  Google Scholar 

  26. Simmons G, Wilkinson D, Reeves JD, Dittmar MT, Beddows S, Weber J, Carnegie G, Desselberger U, Gray PW, Weiss RA, Clapham PR: Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry. J Virol 70: 8355–8360, 1996.

    PubMed  CAS  Google Scholar 

  27. Connor RI, Sheridan KE, Ceradini D, Choe S, Landau NR: Change in coreceptor use correlates with disease progression in HIV-1-infected individuals. J Exp Med 185: 621–628, 1997.

    Article  PubMed  CAS  Google Scholar 

  28. Bjorndal A, Deng H, Jansson M, Fiore JR, Colognesi C, Karlsson A, Albert J, Scarlatti G, Littman DR, Fenyö EM: Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. J Virol 71: 7478–7487, 1997.

    PubMed  CAS  Google Scholar 

  29. Bazan HA, Alkhatib G, Broder CC, Berger EA: Patterns of CCR5, CXCR4 and CCR3 usage by envelope glycoproteins from human immunodeficiency virus type 1 primary isolates. J Virol in press, 1998.

    Google Scholar 

  30. Berger EA, Doms RW, Fenyö EM, Korber BTM, Littman DR, Moore JP, Sattentau QJ, Schuitemaker H, Sodroski J, Weiss RA: Anew classification for HIV-1. Nature 391: 240, 1998.

    Article  PubMed  CAS  Google Scholar 

  31. Alkhatib G, Locati M, Kennedy PE, Murphy PM, Berger EA: HIV-1 coreceptor activity of CCR5 and its inhibition by chemokines: independence from G protein signaling and importance of coreceptor down-modulation. Virology 234: 340–348, 1997.

    Article  PubMed  CAS  Google Scholar 

  32. Weissman D, Rabin RL, Arthos J, Rubbert A, Dybul M, Swofford R, Venkatesan S, Farber JM, Fauci AS: Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor. Nature 389: 981–985, 1997.

    Article  PubMed  CAS  Google Scholar 

  33. Davis CB, Dikic I, Unutmaz D, Hill CM, Arthos J, Siani MA, Thompson DA, Schlessinger J, Littman DR: Signal transduction due to HIV-1 envelope interactions with chemokine receptors CXCR4 or CCR5. J Exp Med 186: 1793–1798, 1997.

    Article  PubMed  CAS  Google Scholar 

  34. Amara A, Gall S, Schwartz O, Salamero J, Montes M, Loetscher P, Baggiolini M, Virelizier J-L, Arenzana-Seisdedos F: HIV coreceptor downregulation as antiviral principle: SDF-1α-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication. J Exp Med 186: 139–146, 1997.

    Article  PubMed  CAS  Google Scholar 

  35. Alkhatib G, Berger EA, Murphy PM, Pease JE: Determinants of HIV-1 coreceptor function on CC chemokine receptor 3: importance of both extracellular and transmembrane/cytoplasmic regions. J Biol Chem 272: 20420–20426, 1997.

    Article  PubMed  CAS  Google Scholar 

  36. Alkhatib G, Ahuja SS, Light D, Mummidi S, Berger EA, Ahuja SK: CC chemokine receptor 5-mediated signaling and HIV-1 co-receptor activity share common structural determinants: critical residues in the third extracellular loop support HIV-1 fusion, J. Biol. Chem. 272:19771–19776. J Biol Chem 272: 19771–19776, 1997.

    Google Scholar 

  37. Hernandez LD, Hoffman LR, Wolfsberg TG, White JM: Virus-cell and cell-cell fusion. Annu Rev Cell Dev Biol 12:627–661, 1996.

    Article  PubMed  CAS  Google Scholar 

  38. Lapham CK, Ouyang J, Chandrasekhar B, Nguyen NY, Dimitrov DS, Golding H: Evidence for cell-surface association between fusin and the CD4-gp120 complex in human cell lines. Science 274: 602–605, 1996.

    Article  PubMed  CAS  Google Scholar 

  39. Wu L, Gerard NP, Wyatt R, Choe H, Parolin C, Ruffing N, Borsetti A, Cardoso AA, Desjardin E, Newman W, Gerard C, Sodroski J: CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature 384: 179–183, 1996.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Edward A. Berger

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  1. Edward A. Berger
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Editors and Affiliations

  1. University of California, Irvine, Irvine, California, USA

    Sudhir Gupta

  2. National Institutes of Health, Bethesda, Maryland, USA

    Alan Sher

  3. Emory University, Atlanta, Georgia, USA

    Rafi Ahmed

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© 1998 Springer Science+Business Media New York

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Berger, E.A. (1998). HIV Entry and Tropism. In: Gupta, S., Sher, A., Ahmed, R. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation VII. Advances in Experimental Medicine and Biology, vol 452. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5355-7_16

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  • DOI: https://doi.org/10.1007/978-1-4615-5355-7_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7443-5

  • Online ISBN: 978-1-4615-5355-7

  • eBook Packages: Springer Book Archive

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