Tenets of protection from progression to AIDS: lessons from the immune responses to HIV-2 infection

References

• UNAIDS. AIDS Epidemic Update: Special Report on HIV/AIDS. Update. AE, Geneva (2006).
   Google Scholar
• Clavel F, Guetard D, Brun-Vezinet F et al. Isolation of a new human retrovirus from West African patients with AIDS. Science233(4761), 343–346 (1986).
   PubMed Web of Science ®Google Scholar
• Quinn TC. Population migration and the spread of types 1 and 2 human immunodeficiency viruses. Proc. Natl Acad. Sci. USA91(7), 2407–2414 (1994).
   PubMed Web of Science ®Google Scholar
• Poulsen AG, Aaby P, Larsen O et al. 9-year HIV-2-associated mortality in an urban community in Bissau, West Africa. Lancet349(9056), 911–914 (1997).
   PubMed Web of Science ®Google Scholar
• Berry N, Jaffar S, Schim van der Loeff M et al. Low level viremia and high CD4% predict normal survival in a cohort of HIV type-2-infected villagers. AIDS Res. Hum. Retroviruses18(16), 1167–1173 (2002).
   PubMedGoogle Scholar
• Alabi AS, Jaffar S, Ariyoshi K et al. Plasma viral load, CD4 cell percentage, HLA and survival of HIV-1, HIV-2, and dually infected Gambian patients. AIDS17(10), 1513–1520 (2003).
   Google Scholar
• Jaffar S, Wilkins A, Ngom PT et al. Rate of decline of percentage CD4+ cells is faster in HIV-1 than in HIV-2 infection. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol.16(5), 327–332 (1997).
   Google Scholar
• Berry N, Ariyoshi K, Jaffar S et al. Low peripheral blood viral HIV-2 RNA in individuals with high CD4 percentage differentiates HIV-2 from HIV-1 infection. J. Hum. Virol.1(7), 457–468 (1998).
   Google Scholar
• Marlink R, Kanki P, Thior I et al. Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science265(5178), 1587–1590 (1994).
   PubMed Web of Science ®Google Scholar
• Martinez-Steele E, Awasana AA, Corrah T et al. Is HIV-2-induced AIDS different from HIV-1-associated AIDS? Data from a West African clinic. AIDS21(3), 317–324 (2007).
   PubMed Web of Science ®Google Scholar
• Whittle H, Egboga A, Todd J et al. Clinical and laboratory predictors of survival in Gambian patients with symptomatic HIV-1 or HIV-2 infection. AIDS6(7), 685–689 (1992).
   PubMedGoogle Scholar
• Schim van der Loeff MF, Jaffar S, Aveika AA et al. Mortality of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients in a clinic-based cohort in The Gambia. AIDS16(13), 1775–1783 (2002).
   PubMed Web of Science ®Google Scholar
• Hansmann A, Schim van der Loeff MF, Kaye S et al. Baseline plasma viral load and CD4 cell percentage predict survival in HIV-1- and HIV-2-infected women in a community-based cohort in The Gambia. J. Acquir. Immune Defic. Syndr.38(3), 335–341 (2005).
   PubMed Web of Science ®Google Scholar
• Travers K, Mboup S, Marlink R et al. Natural protection against HIV-1 infection provided by HIV-2. Science268(5217), 1612–1615 (1995).
   PubMed Web of Science ®Google Scholar
• Norrgren H, Andersson S, Biague AJ et al. Trends and interaction of HIV-1 and HIV-2 in Guinea-Bissau, West Africa: no protection of HIV-2 against HIV-1 infection. AIDS13(6), 701–707 (1999).
   PubMed Web of Science ®Google Scholar
• Wiktor SZ, Nkengasong JN, Ekpini ER et al. Lack of protection against HIV-1 infection among women with HIV-2 infection. AIDS13(6), 695–699 (1999).
   PubMed Web of Science ®Google Scholar
• Schim van der Loeff MF, Aaby P, Aryioshi K et al. HIV-2 does not protect against HIV-1 infection in a rural community in Guinea-Bissau. AIDS15(17), 2303–2310 (2001).
   PubMed Web of Science ®Google Scholar
• Rowland-Jones SL, Whittle HC. Out of Africa: what can we learn from HIV-2 about protective immunity to HIV-1? Nat. Immunol.8(4) 329–331 (2007).
   PubMed Web of Science ®Google Scholar
• Ariyoshi K, Cham F, Berry N et al. HIV-2-specific cytotoxic T-lymphocyte activity is inversely related to proviral load. AIDS9(6), 555–559 (1995).
   Google Scholar
• Sousa AE, Chaves AF, Loureiro A, Victorino RM. Comparison of the frequency of interleukin (IL)-2-, interferon-γ-, and IL-4-producing T cells in 2 diseases, human immunodeficiency virus types 1 and 2, with distinct clinical outcomes. J. Infect. Dis.184(5), 552–559 (2001).
   PubMedGoogle Scholar
• Sousa AE, Carneiro J, Meier-Schellersheim M, Grossman Z, Victorino RM. CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load. J. Immunol.169(6), 3400–3406 (2002).
   PubMed Web of Science ®Google Scholar
• Lopes AR, Jaye A, Dorrell L et al. Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection. J. Immunol.171(1), 307–316 (2003).
   Google Scholar
• Andersson S, Larsen O, Da Silva Z et al. Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau. Clin. Exp. Immunol.139(3), 483–489 (2005).
   Google Scholar
• Duvall MG, Jaye A, Dong T et al. Maintenance of HIV-specific CD4+ T cell help distinguishes HIV-2 from HIV-1 infection. J. Immunol.176(11), 6973–6981 (2006).
   PubMed Web of Science ®Google Scholar
• Nuvor SV, van der Sande M, Rowland-Jones S, Whittle H, Jaye A. Natural killer cell function is well preserved in asymptomatic human immunodeficiency virus type 2 (HIV-2) infection but similar to that of HIV-1 infection when CD4 T-cell counts fall. J. Virol.80(5), 2529–2538 (2006).
   PubMed Web of Science ®Google Scholar
• Alatrakchi N, Damond F, Matheron S et al. Proliferative, IFNg and IL-2-producing T-cell responses to HIV-2 in untreated HIV-2 infection. AIDS20(1), 29–34 (2006).
   Google Scholar
• Leligdowicz A, Yindom LM, Onyango C et al. Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection. J. Clin. Invest.117(10), 3067–3074 (2007).
   PubMed Web of Science ®Google Scholar
• Duvall MG, Precopio ML, Ambrozak DA et al. Polyfunctional T cell responses are a hallmark of HIV-2 infection. Eur. J. Immunol.38350–363 (2008).
   PubMed Web of Science ®Google Scholar
• Larsen O, da Silva Z, Sandstrom A et al. Declining HIV-2 prevalence and incidence among men in a community study from Guinea-Bissau. AIDS12(13), 1707–1714 (1998).
   PubMed Web of Science ®Google Scholar
• Schim van der Loeff MF, Sarge-Njie R, Ceesay S et al. Regional differences in HIV trends in The Gambia: results from sentinel surveillance among pregnant women. AIDS (London, England)17(12), 1841–1846 (2003).
   PubMed Web of Science ®Google Scholar
• van der Loeff MF, Awasana AA, Sarge-Njie R et al. Sixteen years of HIV surveillance in a West African research clinic reveals divergent epidemic trends of HIV-1 and HIV-2. Int. J. Epidemiol.35(5), 1322–1328 (2006).
   PubMed Web of Science ®Google Scholar
• Chen Z, Telfier P, Gettie A et al. Genetic characterization of new West African simian immunodeficiency virus SIVsm: geographic clustering of household-derived SIV strains with human immunodeficiency virus type 2 subtypes and genetically diverse viruses from a single feral sooty mangabey troop. J. Virol.70(6), 3617–3627 (1996).
   PubMed Web of Science ®Google Scholar
• Santiago ML, Range F, Keele BF et al. Simian immunodeficiency virus infection in free-ranging sooty mangabeys (Cercocebus atys atys) from the Tai Forest, Cote d’Ivoire: implications for the origin of epidemic human immunodeficiency virus type 2. J. Virol.79(19), 12515–12527 (2005).
   PubMed Web of Science ®Google Scholar
• Lemey P, Pybus OG, Wang B et al. Tracing the origin and history of the HIV-2 epidemic. Proc. Natl Acad. Sci. USA100(11), 6588–6592 (2003).
   PubMed Web of Science ®Google Scholar
• Schim van der Loeff MF, Aaby P. Towards a better understanding of the epidemiology of HIV-2. AIDS13(Suppl. A), S69–S84 (1999).
   Google Scholar
• Poulsen AG, Aaby P, Gottschau A et al. HIV-2 infection in Bissau, West Africa, 1987–1989: incidence, prevalences, and routes of transmission. J. Acquir. Immune Defic. Syndr.6(8), 941–948 (1993).
   PubMed Web of Science ®Google Scholar
• De Cock KM, Adjorlolo G, Ekpini E et al. Epidemiology and transmission of HIV-2. Why there is no HIV-2 pandemic. JAMA270(17), 2083–2086 (1993).
   PubMed Web of Science ®Google Scholar
• Aaby P, Ariyoshi K, Buckner M et al. Age of wife as a major determinant of male-to-female transmission of HIV-2 infection: a community study from rural West Africa. AIDS10(13), 1585–1590 (1996).
   PubMedGoogle Scholar
• Poulsen AG, Kvinesdal BB, Aaby P et al. Lack of evidence of vertical transmission of human immunodeficiency virus type 2 in a sample of the general population in Bissau. J. Acquir. Immune Defic. Syndr.5(1), 25–30 (1992).
   PubMed Web of Science ®Google Scholar
• Kanki PJ, Travers KU, S MB et al. Slower heterosexual spread of HIV-2 than HIV-1. Lancet343(8903), 943–946 (1994).
   PubMed Web of Science ®Google Scholar
• Adjorlolo-Johnson G, De Cock KM, Ekpini E et al. Prospective comparison of mother-to-child transmission of HIV-1 and HIV-2 in Abidjan, Ivory Coast. JAMA272(6), 462–466 (1994).
   PubMed Web of Science ®Google Scholar
• O’Donovan D, Ariyoshi K, Milligan P et al. Maternal plasma viral RNA levels determine marked differences in mother-to-child transmission rates of HIV-1 and HIV-2 in The Gambia. MRC/Gambia Government/University College London Medical School working group on mother–child transmission of HIV. AIDS14(4), 441–448 (2000).
   PubMed Web of Science ®Google Scholar
• Reeves JD, Doms RW. Human immunodeficiency virus type 2. J. Gen. Virol.83(Pt 6), 1253–1265 (2002).
   PubMed Web of Science ®Google Scholar
• Reeves JD, Hibbitts S, Simmons G et al. Primary human immunodeficiency virus type 2 (HIV-2) isolates infect CD4-negative cells via CCR5 and CXCR4: comparison with HIV-1 and simian immunodeficiency virus and relevance to cell tropism in vivo. J. Virol.73(9), 7795–7804 (1999).
   PubMed Web of Science ®Google Scholar
• McKnight A, Dittmar MT, Moniz-Periera J et al. A broad range of chemokine receptors are used by primary isolates of human immunodeficiency virus type 2 as coreceptors with CD4. J. Virol.72(5), 4065–4071 (1998).
   PubMed Web of Science ®Google Scholar
• Bron R, Klasse PJ, Wilkinson D et al. Promiscuous use of CC and CXC chemokine receptors in cell-to-cell fusion mediated by a human immunodeficiency virus type 2 envelope protein. J. Virol.71(11), 8405–8415 (1997).
   Google Scholar
• Guillon C, van der Ende ME, Boers PH et al. Coreceptor usage of human immunodeficiency virus type 2 primary isolates and biological clones is broad and does not correlate with their syncytium-inducing capacities. J. Virol.72(7), 6260–6263 (1998).
   PubMed Web of Science ®Google Scholar
• Owen SM, Ellenberger D, Rayfield M et al. Genetically divergent strains of human immunodeficiency virus type 2 use multiple coreceptors for viral entry. J. Virol.72(7), 5425–5432 (1998).
   PubMed Web of Science ®Google Scholar
• Morner A, Bjorndal A, Albert J et al. Primary human immunodeficiency virus type 2 (HIV-2) isolates, like HIV-1 isolates, frequently use CCR5 but show promiscuity in coreceptor usage. J. Virol.73(3), 2343–2349 (1999).
   Google Scholar
• Shi Y, Brandin E, Vincic E et al. Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation. J. Gen. Virol.86(Pt 12), 3385–3396 (2005).
   PubMed Web of Science ®Google Scholar
• Ariyoshi K, Berry N, Wilkins A et al. A community-based study of human immunodeficiency virus type 2 provirus load in rural village in West Africa. J. Infect. Dis.173(1), 245–248 (1996).
   Google Scholar
• Popper SJ, Sarr AD, Gueye-Ndiaye A et al. Low plasma human immunodeficiency virus type 2 viral load is independent of proviral load: low virus production in vivo. J. Virol.74(3), 1554–1557 (2000).
   Google Scholar
• MacNeil A, Sarr AD, Sankale JL et al. Direct evidence of lower viral replication rates in vivo in human immunodeficiency virus type 2 (HIV-2) infection than in HIV-1 infection. J. Virol.81(10), 5325–5330 (2007).
   Google Scholar
• Blaak H, Boers PH, Schutten M, van der Enden ME, Osterhaus AD. HIV-2-infected individuals with undetectable plasma viremia carry replication-competent virus in peripheral blood lymphocytes. J. Acquir. Immune Defic. Syndr.36(3), 777–782 (2004).
   PubMed Web of Science ®Google Scholar
• MacNeil A, Sankale JL, Meloni ST et al. Long-term intrapatient viral evolution during HIV-2 infection. J. Infect. Dis.195(5), 726–733 (2007).
   Google Scholar
• Wu L, KewalRamani VN. Dendritic-cell interactions with HIV: infection and viral dissemination. Nat. Rev. Immunol.6(11), 859–868 (2006).
   PubMed Web of Science ®Google Scholar
• Douek DC, Brenchley JM, Betts MR et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature417(6884), 95–98 (2002).
   PubMed Web of Science ®Google Scholar
• Duvall MG, Lore K, Blaak H et al. Dendritic cells are less susceptible to human immunodeficiency virus type 2 (HIV-2) infection than to HIV-1 infection. J. Virol.81(24), 13486–13498 (2007).
   PubMed Web of Science ®Google Scholar
• Guyader M, Emerman M, Sonigo P et al. Genome organization and transactivation of the human immunodeficiency virus type 2. Nature326(6114), 662–669 (1987).
   PubMed Web of Science ®Google Scholar
• Schramm B, Penn ML, Palacios EH et al. Cytopathicity of human immunodeficiency virus type 2 (HIV-2) in human lymphoid tissue is coreceptor dependent and comparable to that of HIV-1. J. Virol.74(20), 9594–9600 (2000).
   Google Scholar
• Whittle HC, Ariyoshi K, Rowland-Jones S. HIV-2 and T cell recognition. Curr. Opin. Immunol.10(4), 382–387 (1998).
   Google Scholar
• Fauci AS, Mavilio D, Kottilil S. NK cells in HIV infection: paradigm for protection or targets for ambush. Nat. Rev. Immunol.5(11), 835–843 (2005).
   PubMed Web of Science ®Google Scholar
• Luban J. Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 Infection. J. Virol.81(3), 1054–1061 (2007).
   PubMed Web of Science ®Google Scholar
• Stremlau M, Owens CM, Perron MJ et al. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature427(6977), 848–853 (2004).
   PubMed Web of Science ®Google Scholar
• Ylinen LM, Keckesova Z, Wilson SJ, Ranasinghe S, Towers GJ. Differential restriction of human immunodeficiency virus type 2 and simian immunodeficiency virus SIVmac by TRIM5α alleles. J. Virol.79(18), 11580–11587 (2005).
   PubMed Web of Science ®Google Scholar
• Song H, Nakayama EE, Yokoyama M et al. A single amino acid of the human immunodeficiency virus type 2 capsid affects its replication in the presence of cynomolgus monkey and human TRIM5α. J. Virol.81(13), 7280–7285 (2007).
   PubMed Web of Science ®Google Scholar
• Brenchley JM, Schacker TW, Ruff LE et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J. Exp. Med.200(6), 749–759 (2004).
   PubMed Web of Science ®Google Scholar
• Mattapallil JJ, Douek DC, Hill B et al. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature434(7037), 1093–1097 (2005).
   PubMed Web of Science ®Google Scholar
• Picker LJ, Watkins DI. HIV pathogenesis: the first cut is the deepest. Nat. Immunol.6(5), 430–432 (2005).
   PubMed Web of Science ®Google Scholar
• Klenerman P, Hill A. T cells and viral persistence: lessons from diverse infections. Nat. Immunol.6(9), 873–879 (2005).
   PubMed Web of Science ®Google Scholar
• Brenchley JM, Price DA, Douek DC. HIV disease: fallout from a mucosal catastrophe? Nat. Immunol.7(3), 235–239 (2006).
   PubMed Web of Science ®Google Scholar
• Papagno L, Spina CA, Marchant A et al. Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol.2(2), E20 (2004).
   PubMed Web of Science ®Google Scholar
• Harari A, Vallelian F, Meylan PR, Pantaleo G. Functional heterogeneity of memory CD4 T cell responses in different conditions of antigen exposure and persistence. J. Immunol.174(2), 1037–1045 (2005).
   PubMed Web of Science ®Google Scholar
• Matloubian M, Concepcion RJ, Ahmed R. CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection. J. Virol.68(12), 8056–8063 (1994).
   PubMed Web of Science ®Google Scholar
• Kostense S, Ogg GS, Manting EH et al. High viral burden in the presence of major HIV-specific CD8+ T cell expansions: evidence for impaired CTL effector function. Eur. J. Immunol.31(3), 677–686 (2001).
   Google Scholar
• Hamilton SE, Wolkers MC, Schoenberger SP, Jameson SC. The generation of protective memory-like CD8+ T cells during homeostatic proliferation requires CD4+ T cells. Nat. Immunol.7(5), 475–481 (2006).
   PubMed Web of Science ®Google Scholar
• Andersson S, Norrgren H, da Silva Z et al. Plasma viral load in HIV-1 and HIV-2 singly and dually infected individuals in Guinea-Bissau, West Africa: significantly lower plasma virus set point in HIV-2 infection than in HIV-1 infection. Arch. Intern. Med.160(21), 3286–3293 (2000).
   PubMed Web of Science ®Google Scholar
• Albuquerque AS, Cortesao CS, Foxall RB et al. Rate of increase in circulating IL-7 and loss of IL-7R{α} expression differ in HIV-1 and HIV-2 infections: two lymphopenic diseases with similar hyperimmune activation but distinct outcomes. J. Immunol.178(5), 3252–3259 (2007).
   Google Scholar
• Silvestri G, Paiardini M, Pandrea I, Lederman MM, Sodora DL. Understanding the benign nature of SIV infection in natural hosts. J. Clin. Invest.117(11), 3148–3154 (2007).
   PubMedGoogle Scholar
• Broussard SR, Staprans SI, White R et al. Simian immunodeficiency virus replicates to high levels in naturally infected African green monkeys without inducing immunologic or neurologic disease. J. Virol.75(5), 2262–2275 (2001).
   PubMedGoogle Scholar
• Gordon SN, Klatt NR, Bosinger SE et al. Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys. J. Immunol.179(5), 3026–3034 (2007).
   PubMed Web of Science ®Google Scholar
• Silvestri G, Sodora DL, Koup RA et al. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity18(3), 441–452 (2003).
   PubMed Web of Science ®Google Scholar
• Walker BD, Chakrabarti S, Moss B et al. HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature328(6128), 345–348 (1987).
   PubMed Web of Science ®Google Scholar
• Koup RA, Safrit JT, Cao Y et al. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J. Virol.68(7), 4650–4655 (1994).
   PubMed Web of Science ®Google Scholar
• Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB. Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J. Virol.68(9), 6103–6110 (1994).
   PubMed Web of Science ®Google Scholar
• Ogg GS, Jin X, Bonhoeffer S et al. Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science279(5359), 2103–2106 (1998).
   PubMed Web of Science ®Google Scholar
• Ogg GS, Kostense S, Klein MR et al. Longitudinal phenotypic analysis of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes: correlation with disease progression. J. Virol.73(11), 9153–9160 (1999).
   PubMed Web of Science ®Google Scholar
• Appay V, Dunbar PR, Callan M et al. Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat. Med.8(4), 379–385 (2002).
   PubMed Web of Science ®Google Scholar
• Jin X, Bauer DE, Tuttleton SE et al. Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques. J. Exp. Med.189(6), 991–998 (1999).
   PubMed Web of Science ®Google Scholar
• Goulder PJ, Phillips RE, Colbert RA et al. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat. Med.3(2), 212–217 (1997).
   PubMed Web of Science ®Google Scholar
• Moore CB, John M, James IR et al. Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science296(5572), 1439–1443 (2002).
   PubMed Web of Science ®Google Scholar
• Grassly NC, Xiang Z, Ariyoshi K et al. Mortality among human immunodeficiency virus type 2-positive villagers in rural Guinea-Bissau is correlated with viral genotype. J. Virol.72(10), 7895–7899 (1998).
   Google Scholar
• Diouf K, Sarr AD, Eisen G et al. Associations between MHC class I and susceptibility to HIV-2 disease progression. J. Hum. Virol.5(1), 1–7 (2002).
   Google Scholar
• Gotch F, McAdam SN, Allsopp CE et al. Cytotoxic T cells in HIV2 seropositive Gambians. J. Immunol.151(6), 3361–3369 (1993).
   Google Scholar
• Rowland-Jones S, Sutton J, Ariyoshi K et al. HIV-specific cytotoxic T-cells in HIV-exposed but uninfected Gambian women. Nat. Med.1(1), 59–64 (1995).
   PubMed Web of Science ®Google Scholar
• Bertoletti A, Cham F, McAdam S et al. Cytotoxic T cells from human immunodeficiency virus type 2-infected patients frequently cross-react with different human immunodeficiency virus type 1 clades. J. Virol.72(3), 2439–2448 (1998).
   Google Scholar
• Rowland-Jones SL, Dong T, Dorrell L et al. Broadly cross-reactive HIV-specific cytotoxic T-lymphocytes in highly-exposed persistently seronegative donors. Immunol. Lett.66(1–3), 9–14 (1999).
   PubMedGoogle Scholar
• Sarr AD, Lu Y, Sankale JL et al. Robust HIV type 2 cellular immune response measured by a modified anthrax toxin-based enzyme-linked immunospot assay. AIDS Res. Hum. Retroviruses17(13), 1257–1264 (2001).
   Google Scholar
• Jaye A, Sarge-Njie R, Schim van der Loeff M et al. No differences in cellular immune responses between asymptomatic HIV type 1- and type 2-infected Gambian patients. J. Infect. Dis.189(3), 498–505 (2004).
   PubMed Web of Science ®Google Scholar
• Betts MR, Ambrozak DR, Douek DC et al. Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses: relationship to viral load in untreated HIV infection. J. Virol.75(24), 11983–11991 (2001).
   PubMed Web of Science ®Google Scholar
• Novitsky V, Cao H, Rybak N et al. Magnitude and frequency of cytotoxic T-lymphocyte responses: identification of immunodominant regions of human immunodeficiency virus type 1 subtype C. J. Virol.76(20), 10155–10168 (2002).
   Google Scholar
• Yu XG, Addo MM, Rosenberg ES et al. Consistent patterns in the development and immunodominance of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T-cell responses following acute HIV-1 infection. J. Virol.76(17), 8690–8701 (2002).
   Google Scholar
• Cao J, McNevin J, Holte S et al. Comprehensive analysis of human immunodeficiency virus type 1 (HIV-1)-specific γ-interferon-secreting CD8+ T cells in primary HIV-1 infection. J. Virol.77(12), 6867–6878 (2003).
   Google Scholar
• Addo MM, Yu XG, Rathod A et al. Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load. J. Virol.77(3), 2081–2092 (2003).
   PubMed Web of Science ®Google Scholar
• Kaufmann DE, Bailey PM, Sidney J et al. Comprehensive analysis of human immunodeficiency virus type 1-specific CD4 responses reveals marked immunodominance of Gag and Nef and the presence of broadly recognized peptides. J. Virol.78(9), 4463–4477 (2004).
   PubMed Web of Science ®Google Scholar
• Masemola A, Mashishi T, Khoury G et al. Hierarchical targeting of subtype C human immunodeficiency virus type 1 proteins by CD8+ T cells: correlation with viral load. J. Virol.78(7), 3233–3243 (2004).
   PubMed Web of Science ®Google Scholar
• Rinaldo C, Huang XL, Fan ZF et al. 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.69(9), 5838–5842 (1995).
   PubMed Web of Science ®Google Scholar
• Kalams SA, Buchbinder SP, Rosenberg ES et al. Association between virus-specific cytotoxic T-lymphocyte and helper responses in human immunodeficiency virus type 1 infection. J. Virol.73(8), 6715–6720 (1999).
   Google Scholar
• Edwards BH, Bansal A, Sabbaj S et al. 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.76(5), 2298–2305 (2002).
   PubMed Web of Science ®Google Scholar
• Goulder PJ, Brander C, Annamalai K et al. Differential narrow focusing of immunodominant human immunodeficiency virus gag-specific cytotoxic T-lymphocyte responses in infected African and caucasoid adults and children. J. Virol.74(12), 5679–5690 (2000).
   Google Scholar
• Novitsky V, Gilbert P, Peter T et al. Association between virus-specific T-cell responses and plasma viral load in human immunodeficiency virus type 1 subtype C infection. J. Virol.77(2), 882–890 (2003).
   Google Scholar
• Ramduth D, Chetty P, Mngquandaniso NC et al. Differential immunogenicity of HIV-1 clade C proteins in eliciting CD8+ and CD4+ cell responses. J. Infect. Dis.192(9), 1588–1596 (2005).
   Google Scholar
• Kiepiela P, Ngumbela K, Thobakgale C et al. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat. Med.13(1), 46–53 (2007).
   PubMed Web of Science ®Google Scholar
• Melamed D, Mark-Danieli M, Kenan-Eichler M et al. The conserved carboxy terminus of the capsid domain of human immunodeficiency virus type 1 Gag protein is important for virion assembly and release. J. Virol.78(18), 9675–9688 (2004).
   Google Scholar
• Martinez-Picado J, Prado JG, Fry EE et al. Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J. Virol.80(7), 3617–3623 (2006).
   PubMed Web of Science ®Google Scholar
• Lichterfeld M, Yu XG, Cohen D et al. HIV-1 Nef is preferentially recognized by CD8 T cells in primary HIV-1 infection despite a relatively high degree of genetic diversity. AIDS18(10), 1383–1392 (2004).
   PubMedGoogle Scholar
• Zheng NN, Kiviat NB, Sow PS et al. Comparison of human immunodeficiency virus (HIV)-specific T-cell responses in HIV-1- and HIV-2-infected individuals in Senegal. J. Virol.78(24), 13934–13942 (2004).
   PubMed Web of Science ®Google Scholar
• Gillespie GM, Pinheiro S, Sayeid-Al-Jamee M et al. CD8+ T cell responses to human immunodeficiency viruses type 2 (HIV-2) and type 1 (HIV-1) Gag proteins are distinguishable by magnitude and breadth but not cellular phenotype. Eur. J. Immunol.35(5), 1445–1453 (2005).
   PubMed Web of Science ®Google Scholar
• Dong T, Stewart-Jones G, Chen N et al. HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor. J. Exp. Med.200(12), 1547–1557 (2004).
   PubMedGoogle Scholar
• Meyer-Olson D, Brady KW, Bartman MT et al. Fluctuations of functionally distinct CD8+ T-cell clonotypes demonstrate flexibility of the HIV-specific TCR repertoire. Blood107(6), 2373–2383 (2006).
   Google Scholar
• Phillips RE, Rowland-Jones S, Nixon DF et al. Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature354(6353), 453–459 (1991).
   PubMed Web of Science ®Google Scholar
• John M, Mallal S. CTL responses to HIV and SIV: wrestling with smoke. Nat. Immunol.6(3), 232–234 (2005).
   Google Scholar
• McMichael AJ, Rowland-Jones SL. Cellular immune responses to HIV. Nature410(6831), 980–987 (2001).
   PubMed Web of Science ®Google Scholar
• Sun JC, Bevan MJ. Defective CD8 T cell memory following acute infection without CD4 T cell help. Science300(5617), 339–342 (2003).
   PubMed Web of Science ®Google Scholar
• Giorgi JV, Hultin LE, McKeating JA et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J. Infect. Dis.179(4), 859–870 (1999).
   PubMed Web of Science ®Google Scholar
• Jaffar S, Van der Loeff MS, Eugen-Olsen J et al. Immunological predictors of survival in HIV type 2-infected rural villagers in Guinea-Bissau. AIDS Res. Hum. Retroviruses21(6), 560–564 (2005).
   PubMed Web of Science ®Google Scholar
• Hanson A, Sarr AD, Shea A et al. Distinct profile of T cell activation in HIV type 2 compared to HIV type 1 infection: differential mechanism for immunoprotection. AIDS Res. Hum. Retroviruses21(9), 791–798 (2005).
   Google Scholar
• Michel P, Balde AT, Roussilhon C et al. Reduced immune activation and T cell apoptosis in human immunodeficiency virus type 2 compared with type 1: correlation of T cell apoptosis with b2 microglobulin concentration and disease evolution. J. Infect. Dis.181(1), 64–75 (2000).
   Google Scholar
• Markovitz DM, Hannibal M, Perez VL et al. Differential regulation of human immunodeficiency viruses (HIVs): a specific regulatory element in HIV-2 responds to stimulation of the T-cell antigen receptor. Proc. Natl Acad. Sci. USA87(23), 9098–9102 (1990).
   PubMedGoogle Scholar
• Hannibal MC, Markovitz DM, Clark N, Nabel GJ. Differential activation of human immunodeficiency virus type 1 and 2 transcription by specific T-cell activation signals. J. Virol.67(8), 5035–5040 (1993).
   PubMed Web of Science ®Google Scholar
• Munch J, Schindler M, Wildum S et al. Primary sooty mangabey simian immunodeficiency virus and human immunodeficiency virus type 2 nef alleles modulate cell surface expression of various human receptors and enhance viral infectivity and replication. J. Virol.79(16), 10547–10560 (2005).
   Google Scholar
• Schindler M, Munch J, Kutsch O et al. Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell125(6), 1055–1067 (2006).
   PubMed Web of Science ®Google Scholar
• Betts MR, Price DA, Brenchley JM et al. The functional profile of primary human antiviral CD8+ T cell effector activity is dictated by cognate peptide concentration. J. Immunol.172(10), 6407–6417 (2004).
   Google Scholar
• Emini EA, Schleif WA, Nunberg JH et al. Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. Nature355(6362), 728–730 (1992).
   PubMed Web of Science ®Google Scholar
• Wei X, Decker JM, Wang S et al. Antibody neutralization and escape by HIV-1. Nature422(6929), 307–312 (2003).
   PubMed Web of Science ®Google Scholar
• Bjorling E, Scarlatti G, von Gegerfelt A et al. Autologous neutralizing antibodies prevail in HIV-2 but not in HIV-1 infection. Virology193(1), 528–530 (1993).
   PubMed Web of Science ®Google Scholar
• Fenyo EM, Putkonen P. Broad cross-neutralizing activity in serum is associated with slow progression and low risk of transmission in primate lentivirus infections. Immunol. Lett.51(1–2), 95–99 (1996).
   Google Scholar
• Witvrouw M, Pannecouque C, Van Laethem K et al. Activity of non-nucleoside reverse transcriptase inhibitors against HIV-2 and SIV. AIDS13(12), 1477–1483 (1999).
   PubMed Web of Science ®Google Scholar
• Colson P, Henry M, Tourres C et al. Polymorphism and drug-selected mutations in the protease gene of human immunodeficiency virus type 2 from patients living in Southern France. J. Clin. Microbiol.42(2), 570–577 (2004).
   PubMed Web of Science ®Google Scholar
• Jallow S, Kaye S, Alabi A et al. Virological and immunological response to Combivir and emergence of drug resistance mutations in a cohort of HIV-2 patients in The Gambia. AIDS20(10), 1455–1458 (2006).
   Google Scholar
• Mullins C, Eisen G, Popper S et al. Highly active antiretroviral therapy and viral response in HIV type 2 infection. Clin. Infect. Dis.38(12), 1771–1779 (2004).
   Google Scholar