Human Immunodeficiency Virus Type 1 (HIV-1)-specific CD8+-T-cell Responses for Groups of HIV-1-infected Individuals with Different HLA-B*35 Genotypes

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2002 Nov 20

PMID 12438586

Citations 30

Authors

Xia Jin

Xiaojiang Gao

Murugappan Ramanathan Jr

Geoffrey R Deschenes

George W Nelson

Stephen J OBrien

James J Goedert

David D Ho

Thomas R OBrien

Mary Carrington

Affiliations

Soon will be listed here.

Abstract

Human immunodeficiency virus type 1 (HIV-1)-infected individuals with HLA-B*35 allelic variants B*3502/3503/3504/5301 (B*35-Px) progress more rapidly to AIDS than do those with B*3501 (B*35-PY). The mechanisms responsible for this phenomenon are not clear. To examine whether cellular immune responses may differ according to HLA-B*35 genotype, we quantified HIV-1-specific CD8(+)-T-cell (CTL) responses using an intracellular cytokine-staining assay with specimens from 32 HIV-1-positive individuals who have B*35 alleles. Among them, 75% had CTL responses to Pol, 69% had CTL responses to Gag, 50% had CTL responses to Nef, and 41% had CTL responses to Env. The overall magnitude of CTL responses did not differ between patients bearing B*35-Px genotypes and those bearing B*35-PY genotypes. A higher percentage of Gag-specific CTL was associated with lower HIV-1 RNA levels (P = 0.009) in individuals with B*35-PY. A negative association between CTL activity for each of the four HIV antigens and viral load was observed among individuals with B*35-PY, and the association reached significance for Gag. No significant relationship between CTL activity and viral load was observed in the B*35-Px group. The relationship between total CTL activity and HIV RNA among B*35-Px carriers differed significantly from that among B*35-PY carriers (P < 0.05). The data are consistent with the hypothesis that higher levels of virus-specific CTL contribute to protection against HIV disease progression in infected individuals with B*35-PY, but not in those with B*35-Px.

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References

Greenough T, Brettler D, Somasundaran M, Panicali D, Sullivan J . Human immunodeficiency virus type 1-specific cytotoxic T lymphocytes (CTL), virus load, and CD4 T cell loss: evidence supporting a protective role for CTL in vivo. J Infect Dis. 1997; 176(1):118-25. DOI: 10.1086/514013. View

Evans D, OConnor D, Jing P, Dzuris J, Sidney J, Da Silva J . Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef. Nat Med. 1999; 5(11):1270-6. DOI: 10.1038/15224. View

Musey L, Hughes J, Schacker T, Shea T, Corey L, McElrath M . Cytotoxic-T-cell responses, viral load, and disease progression in early human immunodeficiency virus type 1 infection. N Engl J Med. 1997; 337(18):1267-74. DOI: 10.1056/NEJM199710303371803. View

Carrington M, OBrien S . The influence of HLA genotype on AIDS. Annu Rev Med. 2003; 54:535-51. DOI: 10.1146/annurev.med.54.101601.152346. View

Koenig S, Conley A, Brewah Y, Jones G, Leath S, Boots L . Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression. Nat Med. 1995; 1(4):330-6. DOI: 10.1038/nm0495-330. View

Carrington M, Nelson G, Martin M, Kissner T, Vlahov D, Goedert J . HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science. 1999; 283(5408):1748-52. DOI: 10.1126/science.283.5408.1748. View

Ogg G, Jin X, Bonhoeffer S, Dunbar P, Nowak M, Monard S . Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science. 1998; 279(5359):2103-6. DOI: 10.1126/science.279.5359.2103. View

Phillips R, Rowland-Jones S, Nixon D, Gotch F, Edwards J, Ogunlesi A . Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature. 1991; 354(6353):453-9. DOI: 10.1038/354453a0. View

Rinaldo C, Huang X, Fan Z, Ding M, BELTZ L, Logar A . High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors. J Virol. 1995; 69(9):5838-42. PMC: 189455. DOI: 10.1128/JVI.69.9.5838-5842.1995. View

10.

Goulder P, Phillips R, Colbert R, McAdam S, Ogg G, Nowak M . Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med. 1997; 3(2):212-7. DOI: 10.1038/nm0297-212. View

11.

Allen T, OConnor D, Jing P, Dzuris J, Mothe B, Vogel T . Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia. Nature. 2000; 407(6802):386-90. DOI: 10.1038/35030124. View

12.

Appay V, Nixon D, Donahoe S, Gillespie G, Dong T, King A . HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function. J Exp Med. 2000; 192(1):63-75. PMC: 1887711. DOI: 10.1084/jem.192.1.63. View

13.

Edwards B, Bansal A, Sabbaj S, Bakari J, Mulligan M, Goepfert P . Magnitude of functional CD8+ T-cell responses to the gag protein of human immunodeficiency virus type 1 correlates inversely with viral load in plasma. J Virol. 2002; 76(5):2298-305. PMC: 135950. DOI: 10.1128/jvi.76.5.2298-2305.2002. View

14.

Borrow P, Lewicki H, Wei X, Horwitz M, Peffer N, Meyers H . Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med. 1997; 3(2):205-11. DOI: 10.1038/nm0297-205. View

15.

OBrien T, Rosenberg P, Yellin F, Goedert J . Longitudinal HIV-1 RNA levels in a cohort of homosexual men. J Acquir Immune Defic Syndr Hum Retrovirol. 1998; 18(2):155-61. DOI: 10.1097/00042560-199806010-00007. View

16.

Goulder P, Bunce M, Krausa P, McIntyre K, Crowley S, Morgan B . Novel, cross-restricted, conserved, and immunodominant cytotoxic T lymphocyte epitopes in slow progressors in HIV type 1 infection. AIDS Res Hum Retroviruses. 1996; 12(18):1691-8. DOI: 10.1089/aid.1996.12.1691. View

17.

Klein M, van Baalen C, Holwerda A, Kerkhof Garde S, Bende R, Keet I . Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics. J Exp Med. 1995; 181(4):1365-72. PMC: 2191947. DOI: 10.1084/jem.181.4.1365. View

18.

Gea-Banacloche J, Migueles S, Martino L, Shupert W, McNeil A, Sabbaghian M . Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors. J Immunol. 2000; 165(2):1082-92. DOI: 10.4049/jimmunol.165.2.1082. View

19.

Haas G, Plikat U, Debre P, Lucchiari M, Katlama C, Dudoit Y . Dynamics of viral variants in HIV-1 Nef and specific cytotoxic T lymphocytes in vivo. J Immunol. 1996; 157(9):4212-21. View

20.

Carmichael A, Jin X, Sissons P, Borysiewicz L . Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein-Barr virus in late disease. J Exp Med. 1993; 177(2):249-56. PMC: 2190885. DOI: 10.1084/jem.177.2.249. View