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. 1997 May;71(5):3932–3939. doi: 10.1128/jvi.71.5.3932-3939.1997

Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection.

B Chackerian 1, E M Long 1, P A Luciw 1, J Overbaugh 1
PMCID: PMC191545  PMID: 9094670

Abstract

Primate lentiviruses use chemokine coreceptors in addition to the CD4 receptor to initiate virus infection. Simian immunodeficiency virus (SIV) productively infects human cells expressing CD4 and the human allele of the chemokine coreceptor CCR-5 as efficiently as it infects macaque cells expressing human CD4, suggesting that SIV can function with either a simian or a human coreceptor in conjunction with human CD4. In the same macaque cells expressing human CD4, the replication of human immunodeficiency virus type 1 (HIV-1) is blocked at several stages of infection; some isolates are restricted prior to reverse transcription, while others, including some macrophage-tropic and primary isolates, are restricted at a step after reverse transcription but prior to migration of the preintegration complex to the nucleus. Both blocks in HIV-1 replication can be relieved by either expression of the appropriate human coreceptor (CCR-5 or CXCR-4) or expression of SIV gene products in cis with the HIV-1 envelope as a chimera between SIV and HIV-1 (SHIV). Thus, a virus with a SIV core and HIV-1 envelope can efficiently infect macaque cells expressing human CD4, presumably by interacting with the simian coreceptor, whereas a virus with an HIV-1 core and an HIV-1 envelope requires expression of the human allele of the coreceptor for productive infection of these cells. These studies suggest that there are interactions among the coreceptor, the viral envelope, and another viral gene product that govern postentry steps of virus replication. These data are consistent with the hypothesis that such interactions may be required for translocation of the virus core to the nucleus. Moreover, the differential abilities of SIV and HIV-1 to function in these processes with heterologous primate coreceptors may have implications for cross-species transmission.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agy M. B., Foy K., Gale M. J., Benveniste R. E., Clark E. A., Katze M. G. Viral and cellular gene expression in CD4+ human lymphoid cell lines infected by the simian immunodeficiency virus, SIV/Mne. Virology. 1991 Jul;183(1):170–180. doi: 10.1016/0042-6822(91)90130-4. [DOI] [PubMed] [Google Scholar]
  2. Alkhatib G., Combadiere C., Broder C. C., Feng Y., Kennedy P. E., Murphy P. M., Berger E. A. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996 Jun 28;272(5270):1955–1958. doi: 10.1126/science.272.5270.1955. [DOI] [PubMed] [Google Scholar]
  3. Berson J. F., Long D., Doranz B. J., Rucker J., Jirik F. R., Doms R. W. A seven-transmembrane domain receptor involved in fusion and entry of T-cell-tropic human immunodeficiency virus type 1 strains. J Virol. 1996 Sep;70(9):6288–6295. doi: 10.1128/jvi.70.9.6288-6295.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boone L. R., Myer F. E., Yang D. M., Ou C. Y., Koh C. K., Roberson L. E., Tennant R. W., Yang W. K. Reversal of Fv-1 host range by in vitro restriction endonuclease fragment exchange between molecular clones of N-tropic and B-tropic murine leukemia virus genomes. J Virol. 1983 Oct;48(1):110–119. doi: 10.1128/jvi.48.1.110-119.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bowerman B., Brown P. O., Bishop J. M., Varmus H. E. A nucleoprotein complex mediates the integration of retroviral DNA. Genes Dev. 1989 Apr;3(4):469–478. doi: 10.1101/gad.3.4.469. [DOI] [PubMed] [Google Scholar]
  6. Bukrinsky M. I., Haggerty S., Dempsey M. P., Sharova N., Adzhubel A., Spitz L., Lewis P., Goldfarb D., Emerman M., Stevenson M. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature. 1993 Oct 14;365(6447):666–669. doi: 10.1038/365666a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Camerini D., Seed B. A CD4 domain important for HIV-mediated syncytium formation lies outside the virus binding site. Cell. 1990 Mar 9;60(5):747–754. doi: 10.1016/0092-8674(90)90089-w. [DOI] [PubMed] [Google Scholar]
  8. Chackerian B., Haigwood N. L., Overbaugh J. Characterization of a CD4-expressing macaque cell line that can detect virus after a single replication cycle and can be infected by diverse simian immunodeficiency virus isolates. Virology. 1995 Nov 10;213(2):386–394. doi: 10.1006/viro.1995.0011. [DOI] [PubMed] [Google Scholar]
  9. Cheng-Mayer C., Quiroga M., Tung J. W., Dina D., Levy J. A. Viral determinants of human immunodeficiency virus type 1 T-cell or macrophage tropism, cytopathogenicity, and CD4 antigen modulation. J Virol. 1990 Sep;64(9):4390–4398. doi: 10.1128/jvi.64.9.4390-4398.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Choe H., Farzan M., Sun Y., Sullivan N., Rollins B., Ponath P. D., Wu L., Mackay C. R., LaRosa G., Newman W. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell. 1996 Jun 28;85(7):1135–1148. doi: 10.1016/s0092-8674(00)81313-6. [DOI] [PubMed] [Google Scholar]
  11. Clapham P. R., Blanc D., Weiss R. A. Specific cell surface requirements for the infection of CD4-positive cells by human immunodeficiency virus types 1 and 2 and by Simian immunodeficiency virus. Virology. 1991 Apr;181(2):703–715. doi: 10.1016/0042-6822(91)90904-P. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cocchi F., DeVico A. L., Garzino-Demo A., Arya S. K., Gallo R. C., Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995 Dec 15;270(5243):1811–1815. doi: 10.1126/science.270.5243.1811. [DOI] [PubMed] [Google Scholar]
  13. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  14. Deng H., Liu R., Ellmeier W., Choe S., Unutmaz D., Burkhart M., Di Marzio P., Marmon S., Sutton R. E., Hill C. M. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun 20;381(6584):661–666. doi: 10.1038/381661a0. [DOI] [PubMed] [Google Scholar]
  15. Doranz B. J., Rucker J., Yi Y., Smyth R. J., Samson M., Peiper S. C., Parmentier M., Collman R. G., Doms R. W. 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. 1996 Jun 28;85(7):1149–1158. doi: 10.1016/s0092-8674(00)81314-8. [DOI] [PubMed] [Google Scholar]
  16. Dragic T., Litwin V., Allaway G. P., Martin S. R., Huang Y., Nagashima K. A., Cayanan C., Maddon P. J., Koup R. A., Moore J. P. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996 Jun 20;381(6584):667–673. doi: 10.1038/381667a0. [DOI] [PubMed] [Google Scholar]
  17. Endres M. J., Clapham P. R., Marsh M., Ahuja M., Turner J. D., McKnight A., Thomas J. F., Stoebenau-Haggarty B., Choe S., Vance P. J. CD4-independent infection by HIV-2 is mediated by fusin/CXCR4. Cell. 1996 Nov 15;87(4):745–756. doi: 10.1016/s0092-8674(00)81393-8. [DOI] [PubMed] [Google Scholar]
  18. Fauci A. S. Host factors and the pathogenesis of HIV-induced disease. Nature. 1996 Dec 12;384(6609):529–534. doi: 10.1038/384529a0. [DOI] [PubMed] [Google Scholar]
  19. Feng Y., Broder C. C., Kennedy P. E., Berger E. A. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996 May 10;272(5263):872–877. doi: 10.1126/science.272.5263.872. [DOI] [PubMed] [Google Scholar]
  20. Franke E. K., Yuan H. E., Luban J. Specific incorporation of cyclophilin A into HIV-1 virions. Nature. 1994 Nov 24;372(6504):359–362. doi: 10.1038/372359a0. [DOI] [PubMed] [Google Scholar]
  21. Gallay P., Swingler S., Aiken C., Trono D. HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator. Cell. 1995 Feb 10;80(3):379–388. doi: 10.1016/0092-8674(95)90488-3. [DOI] [PubMed] [Google Scholar]
  22. Himathongkham S., Luciw P. A. Restriction of HIV-1 (subtype B) replication at the entry step in rhesus macaque cells. Virology. 1996 May 15;219(2):485–488. doi: 10.1006/viro.1996.0276. [DOI] [PubMed] [Google Scholar]
  23. Horuk R. Molecular properties of the chemokine receptor family. Trends Pharmacol Sci. 1994 May;15(5):159–165. doi: 10.1016/0165-6147(94)90077-9. [DOI] [PubMed] [Google Scholar]
  24. Huang Z. B., Potash M. J., Simm M., Shahabuddin M., Chao W., Gendelman H. E., Eden E., Volsky D. J. Infection of macrophages with lymphotropic human immunodeficiency virus type 1 can be arrested after viral DNA synthesis. J Virol. 1993 Nov;67(11):6893–6896. doi: 10.1128/jvi.67.11.6893-6896.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kestler H., Kodama T., Ringler D., Marthas M., Pedersen N., Lackner A., Regier D., Sehgal P., Daniel M., King N. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science. 1990 Jun 1;248(4959):1109–1112. doi: 10.1126/science.2160735. [DOI] [PubMed] [Google Scholar]
  26. Kimpton J., Emerman M. Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene. J Virol. 1992 Apr;66(4):2232–2239. doi: 10.1128/jvi.66.4.2232-2239.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  28. Koenig S., Hirsch V. M., Olmsted R. A., Powell D., Maury W., Rabson A., Fauci A. S., Purcell R. H., Johnson P. R. Selective infection of human CD4+ cells by simian immunodeficiency virus: productive infection associated with envelope glycoprotein-induced fusion. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2443–2447. doi: 10.1073/pnas.86.7.2443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lapham C. K., Ouyang J., Chandrasekhar B., Nguyen N. Y., Dimitrov D. S., Golding H. Evidence for cell-surface association between fusin and the CD4-gp120 complex in human cell lines. Science. 1996 Oct 25;274(5287):602–605. doi: 10.1126/science.274.5287.602. [DOI] [PubMed] [Google Scholar]
  30. Levy J. A., Shimabukuro J., McHugh T., Casavant C., Stites D., Oshiro L. AIDS-associated retroviruses (ARV) can productively infect other cells besides human T helper cells. Virology. 1985 Dec;147(2):441–448. doi: 10.1016/0042-6822(85)90146-1. [DOI] [PubMed] [Google Scholar]
  31. Li J. T., Halloran M., Lord C. I., Watson A., Ranchalis J., Fung M., Letvin N. L., Sodroski J. G. Persistent infection of macaques with simian-human immunodeficiency viruses. J Virol. 1995 Nov;69(11):7061–7067. doi: 10.1128/jvi.69.11.7061-7067.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Li J., Lord C. I., Haseltine W., Letvin N. L., Sodroski J. Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. J Acquir Immune Defic Syndr. 1992;5(7):639–646. [PubMed] [Google Scholar]
  33. Lori F., di Marzo Veronese F., de Vico A. L., Lusso P., Reitz M. S., Jr, Gallo R. C. Viral DNA carried by human immunodeficiency virus type 1 virions. J Virol. 1992 Aug;66(8):5067–5074. doi: 10.1128/jvi.66.8.5067-5074.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Luban J., Bossolt K. L., Franke E. K., Kalpana G. V., Goff S. P. Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B. Cell. 1993 Jun 18;73(6):1067–1078. doi: 10.1016/0092-8674(93)90637-6. [DOI] [PubMed] [Google Scholar]
  35. Luciw P. A., Pratt-Lowe E., Shaw K. E., Levy J. A., Cheng-Mayer C. Persistent infection of rhesus macaques with T-cell-line-tropic and macrophage-tropic clones of simian/human immunodeficiency viruses (SHIV). Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7490–7494. doi: 10.1073/pnas.92.16.7490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell. 1986 Nov 7;47(3):333–348. doi: 10.1016/0092-8674(86)90590-8. [DOI] [PubMed] [Google Scholar]
  37. McClure M. O., Sattentau Q. J., Beverley P. C., Hearn J. P., Fitzgerald A. K., Zuckerman A. J., Weiss R. A. HIV infection of primate lymphocytes and conservation of the CD4 receptor. Nature. 1987 Dec 3;330(6147):487–489. doi: 10.1038/330487a0. [DOI] [PubMed] [Google Scholar]
  38. McDougal J. S., Nicholson J. K., Cross G. D., Cort S. P., Kennedy M. S., Mawle A. C. Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. J Immunol. 1986 Nov 1;137(9):2937–2944. [PubMed] [Google Scholar]
  39. Miller A. D., Rosman G. J. Improved retroviral vectors for gene transfer and expression. Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90. [PMC free article] [PubMed] [Google Scholar]
  40. Mori K., Ringler D. J., Desrosiers R. C. Restricted replication of simian immunodeficiency virus strain 239 in macrophages is determined by env but is not due to restricted entry. J Virol. 1993 May;67(5):2807–2814. doi: 10.1128/jvi.67.5.2807-2814.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Morrow W. J., Homsy J., Eichberg J. W., Krowka J., Pan L. Z., Gaston I., Legg H., Lerche N., Thomas J., Levy J. A. Long-term observation of baboons, rhesus monkeys, and chimpanzees inoculated with HIV and given periodic immunosuppressive treatment. AIDS Res Hum Retroviruses. 1989 Apr;5(2):233–245. doi: 10.1089/aid.1989.5.233. [DOI] [PubMed] [Google Scholar]
  42. Moss G. B., Overbaugh J., Welch M., Reilly M., Bwayo J., Plummer F. A., Ndinya-Achola J. O., Malisa M. A., Kreiss J. K. Human immunodeficiency virus DNA in urethral secretions in men: association with gonococcal urethritis and CD4 cell depletion. J Infect Dis. 1995 Dec;172(6):1469–1474. doi: 10.1093/infdis/172.6.1469. [DOI] [PubMed] [Google Scholar]
  43. Murphy P. M. The molecular biology of leukocyte chemoattractant receptors. Annu Rev Immunol. 1994;12:593–633. doi: 10.1146/annurev.iy.12.040194.003113. [DOI] [PubMed] [Google Scholar]
  44. Samson M., Labbe O., Mollereau C., Vassart G., Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry. 1996 Mar 19;35(11):3362–3367. doi: 10.1021/bi952950g. [DOI] [PubMed] [Google Scholar]
  45. Sattentau Q. J., Clapham P. R., Weiss R. A., Beverley P. C., Montagnier L., Alhalabi M. F., Gluckmann J. C., Klatzmann D. The human and simian immunodeficiency viruses HIV-1, HIV-2 and SIV interact with similar epitopes on their cellular receptor, the CD4 molecule. AIDS. 1988 Apr;2(2):101–105. doi: 10.1097/00002030-198804000-00005. [DOI] [PubMed] [Google Scholar]
  46. Schmidtmayerova H., Bolmont C., Baghdiguian S., Hirsch I., Chermann J. C. Distinctive pattern of infection and replication of HIV1 strains in blood-derived macrophages. Virology. 1992 Sep;190(1):124–133. doi: 10.1016/0042-6822(92)91198-4. [DOI] [PubMed] [Google Scholar]
  47. Shibata R., Kawamura M., Sakai H., Hayami M., Ishimoto A., Adachi A. Generation of a chimeric human and simian immunodeficiency virus infectious to monkey peripheral blood mononuclear cells. J Virol. 1991 Jul;65(7):3514–3520. doi: 10.1128/jvi.65.7.3514-3520.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Shibata R., Sakai H., Kawamura M., Tokunaga K., Adachi A. Early replication block of human immunodeficiency virus type 1 in monkey cells. J Gen Virol. 1995 Nov;76(Pt 11):2723–2730. doi: 10.1099/0022-1317-76-11-2723. [DOI] [PubMed] [Google Scholar]
  49. Thali M., Bukovsky A., Kondo E., Rosenwirth B., Walsh C. T., Sodroski J., Göttlinger H. G. Functional association of cyclophilin A with HIV-1 virions. Nature. 1994 Nov 24;372(6504):363–365. doi: 10.1038/372363a0. [DOI] [PubMed] [Google Scholar]
  50. Trono D. Partial reverse transcripts in virions from human immunodeficiency and murine leukemia viruses. J Virol. 1992 Aug;66(8):4893–4900. doi: 10.1128/jvi.66.8.4893-4900.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. York-Higgins D., Cheng-Mayer C., Bauer D., Levy J. A., Dina D. Human immunodeficiency virus type 1 cellular host range, replication, and cytopathicity are linked to the envelope region of the viral genome. J Virol. 1990 Aug;64(8):4016–4020. doi: 10.1128/jvi.64.8.4016-4020.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]

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