Abstract
The chemokine receptors CCR-5 and CXCR-4, and possibly CCR-3, are the principal human immunodeficiency virus type 1 (HIV-1) coreceptors, apparently interacting with HIV-1 envelope, in association with CD4. Cell lines coexpressing CD4 and these chemokine receptors were infected with a panel of seven primary HIV-2 isolates passaged in peripheral blood mononuclear cells (PBMC) and three laboratory HIV-2 strains passaged in T-cell lines. The CCR-5, CCR-3, and CXCR-4 coreceptors could all be used by HIV-2. The ability to use CXCR-4 represents a major difference between HIV-2 and the closely related simian immunodeficiency viruses. Most HIV-2 strains using CCR-5 could also use CCR-3, sometimes with similar efficiencies. As observed for HIV-1, the usage of CCR-5 or CCR-3 was observed principally for HIV-2 strains derived from asymptomatic individuals, while HIV-2 strains derived from AIDS patients used CXCR-4. However, there were several exceptions, and the patterns of coreceptor usage seemed more complex for HIV-2 than for HIV-1. The two T-tropic HIV-2 strains tested used CXCR-4 and not CCR-5, while T-tropic HIV-1 can generally use both. Moreover, among five primary HIV-2 strains all unable to use CXCR-4, three could replicate in CCR-5-negative PBMC, which has not been reported for HIV-1. These observations suggest that the CCR-5 coreceptor is less important for HIV-2 than for HIV-1 and indicate that HIV-2 can use other cell entry pathways and probably other coreceptors. One HIV-2 isolate replicating in normal or CCR-5-negative PBMC failed to infect CXCR-4+ cells or the U87MG-CD4 and sMAGI cell lines, which are permissive to infection by HIV-2 but not by HIV-1. This suggests the existence of several HIV-2-specific coreceptors, which are differentially expressed in cell lines and PBMC.
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Selected References
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- Biti R., Ffrench R., Young J., Bennetts B., Stewart G., Liang T. HIV-1 infection in an individual homozygous for the CCR5 deletion allele. Nat Med. 1997 Mar;3(3):252–253. doi: 10.1038/nm0397-252. [DOI] [PubMed] [Google Scholar]
- Bleul C. C., Wu L., Hoxie J. A., Springer T. A., Mackay C. R. The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1925–1930. doi: 10.1073/pnas.94.5.1925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brelot A., Heveker N., Pleskoff O., Sol N., Alizon M. Role of the first and third extracellular domains of CXCR-4 in human immunodeficiency virus coreceptor activity. J Virol. 1997 Jun;71(6):4744–4751. doi: 10.1128/jvi.71.6.4744-4751.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Chackerian B., Long E. M., Luciw P. A., Overbaugh J. Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection. J Virol. 1997 May;71(5):3932–3939. doi: 10.1128/jvi.71.5.3932-3939.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen Z., Zhou P., Ho D. D., Landau N. R., Marx P. A. Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry. J Virol. 1997 Apr;71(4):2705–2714. doi: 10.1128/jvi.71.4.2705-2714.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chesebro B., Buller R., Portis J., Wehrly K. Failure of human immunodeficiency virus entry and infection in CD4-positive human brain and skin cells. J Virol. 1990 Jan;64(1):215–221. doi: 10.1128/jvi.64.1.215-221.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Clapham P. R., McKnight A., Weiss R. A. Human immunodeficiency virus type 2 infection and fusion of CD4-negative human cell lines: induction and enhancement by soluble CD4. J Virol. 1992 Jun;66(6):3531–3537. doi: 10.1128/jvi.66.6.3531-3537.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clavel F., Charneau P. Fusion from without directed by human immunodeficiency virus particles. J Virol. 1994 Feb;68(2):1179–1185. doi: 10.1128/jvi.68.2.1179-1185.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Connor R. I., Sheridan K. E., Ceradini D., Choe S., Landau N. R. Change in coreceptor use correlates with disease progression in HIV-1--infected individuals. J Exp Med. 1997 Feb 17;185(4):621–628. doi: 10.1084/jem.185.4.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dean M., Carrington M., Winkler C., Huttley G. A., Smith M. W., Allikmets R., Goedert J. J., Buchbinder S. P., Vittinghoff E., Gomperts E. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science. 1996 Sep 27;273(5283):1856–1862. doi: 10.1126/science.273.5283.1856. [DOI] [PubMed] [Google Scholar]
- Deng H. K., Unutmaz D., KewalRamani V. N., Littman D. R. Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature. 1997 Jul 17;388(6639):296–300. doi: 10.1038/40894. [DOI] [PubMed] [Google Scholar]
- 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]
- Dittmar M. T., McKnight A., Simmons G., Clapham P. R., Weiss R. A., Simmonds P. HIV-1 tropism and co-receptor use. Nature. 1997 Feb 6;385(6616):495–496. doi: 10.1038/385495a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Edinger A. L., Amedee A., Miller K., Doranz B. J., Endres M., Sharron M., Samson M., Lu Z. H., Clements J. E., Murphey-Corb M. Differential utilization of CCR5 by macrophage and T cell tropic simian immunodeficiency virus strains. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4005–4010. doi: 10.1073/pnas.94.8.4005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Gao F., Yue L., Robertson D. L., Hill S. C., Hui H., Biggar R. J., Neequaye A. E., Whelan T. M., Ho D. D., Shaw G. M. Genetic diversity of human immunodeficiency virus type 2: evidence for distinct sequence subtypes with differences in virus biology. J Virol. 1994 Nov;68(11):7433–7447. doi: 10.1128/jvi.68.11.7433-7447.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harrington R. D., Geballe A. P. Cofactor requirement for human immunodeficiency virus type 1 entry into a CD4-expressing human cell line. J Virol. 1993 Oct;67(10):5939–5947. doi: 10.1128/jvi.67.10.5939-5947.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- He J., Chen Y., Farzan M., Choe H., Ohagen A., Gartner S., Busciglio J., Yang X., Hofmann W., Newman W. CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature. 1997 Feb 13;385(6617):645–649. doi: 10.1038/385645a0. [DOI] [PubMed] [Google Scholar]
- Huang Y., Paxton W. A., Wolinsky S. M., Neumann A. U., Zhang L., He T., Kang S., Ceradini D., Jin Z., Yazdanbakhsh K. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996 Nov;2(11):1240–1243. doi: 10.1038/nm1196-1240. [DOI] [PubMed] [Google Scholar]
- Koot M., Vos A. H., Keet R. P., de Goede R. E., Dercksen M. W., Terpstra F. G., Coutinho R. A., Miedema F., Tersmette M. HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay. AIDS. 1992 Jan;6(1):49–54. doi: 10.1097/00002030-199201000-00006. [DOI] [PubMed] [Google Scholar]
- Li Y., Hui H., Burgess C. J., Price R. W., Sharp P. M., Hahn B. H., Shaw G. M. Complete nucleotide sequence, genome organization, and biological properties of human immunodeficiency virus type 1 in vivo: evidence for limited defectiveness and complementation. J Virol. 1992 Nov;66(11):6587–6600. doi: 10.1128/jvi.66.11.6587-6600.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liao F., Alkhatib G., Peden K. W., Sharma G., Berger E. A., Farber J. M. 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 Jun 2;185(11):2015–2023. doi: 10.1084/jem.185.11.2015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu R., Paxton W. A., Choe S., Ceradini D., Martin S. R., Horuk R., MacDonald M. E., Stuhlmann H., Koup R. A., Landau N. R. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996 Aug 9;86(3):367–377. doi: 10.1016/s0092-8674(00)80110-5. [DOI] [PubMed] [Google Scholar]
- Markovitz D. M. Infection with the human immunodeficiency virus type 2. Ann Intern Med. 1993 Feb 1;118(3):211–218. doi: 10.7326/0003-4819-118-3-199302010-00010. [DOI] [PubMed] [Google Scholar]
- McKnight A., Clapham P. R., Weiss R. A. HIV-2 and SIV infection of nonprimate cell lines expressing human CD4: restrictions to replication at distinct stages. Virology. 1994 May 15;201(1):8–18. doi: 10.1006/viro.1994.1260. [DOI] [PubMed] [Google Scholar]
- McKnight A., Wilkinson D., Simmons G., Talbot S., Picard L., Ahuja M., Marsh M., Hoxie J. A., Clapham P. R. Inhibition of human immunodeficiency virus fusion by a monoclonal antibody to a coreceptor (CXCR4) is both cell type and virus strain dependent. J Virol. 1997 Feb;71(2):1692–1696. doi: 10.1128/jvi.71.2.1692-1696.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore J. P., Trkola A., Dragic T. Co-receptors for HIV-1 entry. Curr Opin Immunol. 1997 Aug;9(4):551–562. doi: 10.1016/s0952-7915(97)80110-0. [DOI] [PubMed] [Google Scholar]
- O'Brien T. R., Winkler C., Dean M., Nelson J. A., Carrington M., Michael N. L., White G. C., 2nd HIV-1 infection in a man homozygous for CCR5 delta 32. Lancet. 1997 Apr 26;349(9060):1219–1219. doi: 10.1016/s0140-6736(97)24017-1. [DOI] [PubMed] [Google Scholar]
- Palermo D. P., DeGraaf M. E., Marotti K. R., Rehberg E., Post L. E. Production of analytical quantities of recombinant proteins in Chinese hamster ovary cells using sodium butyrate to elevate gene expression. J Biotechnol. 1991 Jun;19(1):35–47. doi: 10.1016/0168-1656(91)90073-5. [DOI] [PubMed] [Google Scholar]
- Peden K., Emerman M., Montagnier L. Changes in growth properties on passage in tissue culture of viruses derived from infectious molecular clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI. Virology. 1991 Dec;185(2):661–672. doi: 10.1016/0042-6822(91)90537-l. [DOI] [PubMed] [Google Scholar]
- Pleskoff O., Sol N., Labrosse B., Alizon M. Human immunodeficiency virus strains differ in their ability to infect CD4+ cells expressing the rat homolog of CXCR-4 (fusin). J Virol. 1997 Apr;71(4):3259–3262. doi: 10.1128/jvi.71.4.3259-3262.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pleskoff O., Tréboute C., Brelot A., Heveker N., Seman M., Alizon M. Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry. Science. 1997 Jun 20;276(5320):1874–1878. doi: 10.1126/science.276.5320.1874. [DOI] [PubMed] [Google Scholar]
- Ponath P. D., Qin S., Post T. W., Wang J., Wu L., Gerard N. P., Newman W., Gerard C., Mackay C. R. Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J Exp Med. 1996 Jun 1;183(6):2437–2448. doi: 10.1084/jem.183.6.2437. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reeves J. D., McKnight A., Potempa S., Simmons G., Gray P. W., Power C. A., Wells T., Weiss R. A., Talbot S. J. CD4-independent infection by HIV-2 (ROD/B): use of the 7-transmembrane receptors CXCR-4, CCR-3, and V28 for entry. Virology. 1997 Apr 28;231(1):130–134. doi: 10.1006/viro.1997.8508. [DOI] [PubMed] [Google Scholar]
- Rey-Cuille M. A., Galabru J., Laurent-Crawford A., Krust B., Montagnier L., Hovanessian A. G. HIV-2 EHO isolate has a divergent envelope gene and induces single cell killing by apoptosis. Virology. 1994 Jul;202(1):471–476. doi: 10.1006/viro.1994.1364. [DOI] [PubMed] [Google Scholar]
- Ryan-Graham M. A., Peden K. W. Both virus and host components are important for the manifestation of a Nef- phenotype in HIV-1 and HIV-2. Virology. 1995 Oct 20;213(1):158–168. doi: 10.1006/viro.1995.1556. [DOI] [PubMed] [Google Scholar]
- Samson M., Libert F., Doranz B. J., Rucker J., Liesnard C., Farber C. M., Saragosti S., Lapoumeroulie C., Cognaux J., Forceille C. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996 Aug 22;382(6593):722–725. doi: 10.1038/382722a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Schwartz O., Henin Y., Marechal V., Montagnier L. A rapid and simple colorimetric test for the study of anti-HIV agents. AIDS Res Hum Retroviruses. 1988 Dec;4(6):441–448. doi: 10.1089/aid.1988.4.441. [DOI] [PubMed] [Google Scholar]
- Simmons G., Wilkinson D., Reeves J. D., Dittmar M. T., Beddows S., Weber J., Carnegie G., Desselberger U., Gray P. W., Weiss R. A. 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. 1996 Dec;70(12):8355–8360. doi: 10.1128/jvi.70.12.8355-8360.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strizki J. M., Turner J. D., Collman R. G., Hoxie J., González-Scarano F. A monoclonal antibody (12G5) directed against CXCR-4 inhibits infection with the dual-tropic human immunodeficiency virus type 1 isolate HIV-1(89.6) but not the T-tropic isolate HIV-1(HxB). J Virol. 1997 Jul;71(7):5678–5683. doi: 10.1128/jvi.71.7.5678-5683.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Theodorou I., Meyer L., Magierowska M., Katlama C., Rouzioux C. HIV-1 infection in an individual homozygous for CCR5 delta 32. Seroco Study Group. Lancet. 1997 Apr 26;349(9060):1219–1220. [PubMed] [Google Scholar]
- Westervelt P., Gendelman H. E., Ratner L. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097–3101. doi: 10.1073/pnas.88.8.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamamoto N., Okada M., Koyanagi Y., Kannagi M., Hinuma Y. Transformation of human leukocytes by cocultivation with an adult T cell leukemia virus producer cell line. Science. 1982 Aug 20;217(4561):737–739. doi: 10.1126/science.6980467. [DOI] [PubMed] [Google Scholar]
- Zhang L., Huang Y., He T., Cao Y., Ho D. D. HIV-1 subtype and second-receptor use. Nature. 1996 Oct 31;383(6603):768–768. doi: 10.1038/383768a0. [DOI] [PubMed] [Google Scholar]