Skip to main content
SpringerLink
Log in

The Cellular Immune Response to HIV-2 Infection

  • Living reference work entry
  • First Online:
Encyclopedia of AIDS

  • 224 Accesses

Definition

T-cells play a central role in both the control and pathogenesis of HIV infection. While T-cell responses against HIV-1 infection have been studied in great detail, much less is known about T-cells in the context of HIV-2. This entry summarizes current understanding of the quantitative and qualitative characteristics of HIV-2-specific CD8+ and CD4+ T-cell responses, highlighting key areas in which they may differ from responses against HIV-1, and the clinical implications of such disparities.

Introduction

Although HIV-1 and HIV-2 share substantial similarity in terms of genome and life cycle, there are clear epidemiological and prognostic distinctions between them. An important distinguishing feature of infection is the distribution and time to clinical progression (Marlink et al. 1994). In contrast to HIV-1 infection, where the overwhelming majority of treatment-naïve patients develop AIDS within approximately a decade, the outcome of HIV-2 infection follows an unusual...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Ahmed RKS, Nilsson C, Wang YF, Lehner T, Biberfeld G, Thorstensson R. Beta-chemokine production in macaques vaccinated with live attenuated virus correlates with protection against simian immunodeficiency virus (SIVsm) challenge. J Gen Virol. 1999;80:1569–74.

    Article  CAS  PubMed  Google Scholar 

  • Ahmed RKS, Mäkitalo B, Karlén K, Nilsson C, Biberfeld G, Thorstensson R. Spontaneous production of RANTES and antigen-specific IFN-γ production in macaques vaccinated with SHIV-4 correlates with protection against SIVsm challenge. Clin Exp Immunol. 2002;129:11–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ahmed RK, Norrgren H, da Silva Z, Blaxhult A, Fredriksson EL, Biberfeld G, Andersson S, Thorstensson R. Antigen-specific beta-chemokine production and CD8 T-cell noncytotoxic antiviral activity in HIV-2-infected individuals. Scand J Immunol. 2005;61:63–71.

    Article  CAS  PubMed  Google Scholar 

  • Alatrakchi N, Damond F, Matheron S, Beretta-Tempelhoff S, Campa P, Carcelain G, Brun-Vezinet F, Autran B. Proliferative, IFN gamma and IL-2-producing T-cell responses to HIV-2 in untreated HIV-2 infection. AIDS. 2006;20:29–34.

    Article  CAS  PubMed  Google Scholar 

  • Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996;272:1955–8.

    Article  CAS  PubMed  Google Scholar 

  • Andersson S, Norrgren H, da Silva Z, Biague A, Bamba S, Kwok S, Christopherson C, Biberfeld G, Albert J. 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. 2000;160:3286–93.

    Article  CAS  PubMed  Google Scholar 

  • Appay V, Dunbar PR, Callan M, Klenerman P, Gillespie GM, Papagno L, Ogg GS, King A, Lechner F, Spina CA, et al. Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med. 2002;8:379–85.

    Article  CAS  PubMed  Google Scholar 

  • Ariyoshi K, Cham F, Berry N, Jaffar S, Sabally S, Corrah T, Whittle H. HIV-2-specific cytotoxic T-lymphocyte activity is inversely related to proviral load. AIDS. 1995;9:555–9.

    Article  CAS  PubMed  Google Scholar 

  • Ariyoshi K, Jaffar S, Alabi AS, Berry N, Schim van der Loeff M, Sabally S, N’Gom PT, Corrah T, Tedder R, Whittle H. Plasma RNA viral load predicts the rate of CD4 T cell decline and death in HIV-2-infected patients in West Africa. AIDS. 2000;14:339–44.

    Article  CAS  PubMed  Google Scholar 

  • Berry N, Jaffar S, Van der Loeff MS, Ariyoshi K, Harding E, N’Gom PT, Dias F, Wilkins A, Ricard D, Aaby P, et al. Low level viremia and high CD4% predict normal survival in a cohort of HIV type-2-infected villagers. AIDS Res Hum Retroviruses. 2002;18:1167–73.

    Article  PubMed  Google Scholar 

  • Bertoletti A, Cham F, McAdam S, Rostron T, Rowland-Jones S, Sabally S, Corrah T, Ariyoshi K, Whittle H. Cytotoxic T cells from human immunodeficiency virus type 2-infected patients frequently cross-react with different human immunodeficiency virus type 1 clades. J Virol. 1998;72:2439–48.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Blackbourn DJ, Locher CP, Ramachandran B, Barnett SW, Murthy KK, Carey KD, Brasky KM, Levy JA. CD8+ cells from HIV-2-infected baboons control HIV replication. AIDS. 1997;11:737–46.

    Article  CAS  PubMed  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. 1994;68:6103–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Brun-Vezinet F, Katlama C, Roulot D, Lenoble L, Alizon M, Madjar JJ, Rey MA, Girard PM, Yeni P, Clavel F, et al. Lymphadenopathy-associated virus type 2 in AIDS and AIDS-related complex. Lancet. 1987;329:128–32.

    Article  Google Scholar 

  • Clavel F, Mansinho K, Chamaret S, Guetard D, Favier V, Nina J, Santos-Ferreira MO, Champalimaud JL, Montagnier L. Human immunodeficiency virus type 2 infection associated with AIDS in West Africa. N Engl J Med. 1987;316:1180–5.

    Article  CAS  PubMed  Google Scholar 

  • Cocchi F, DeVico AL, Garzino-Demo A, Cara A, Gallo RC, Lusso P. The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. Nat Med. 1996;2:1244–7.

    Article  CAS  PubMed  Google Scholar 

  • Cocchi F, DeVico AL, Yarchoan R, Redfield R, Cleghorn F, Blattner WA, Garzino-Demo A, Colombini-Hatch S, Margolis D, Gallo RC. Higher macrophage inflammatory protein (MIP)-1α and MIP-1β levels from CD8(+) T cells are associated with asymptomatic HIV-1 infection. Proc Natl Acad Sci U S A. 2000;97:13812–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cordeil S, Nguyen XN, Berger G, Durand S, Ainouze M, Cimarelli A. Evidence for a different susceptibility of primate lentiviruses to type I interferons. J Virol. 2013;87:2587–96.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • de Silva T, Leligdowicz A, Rowland-Jones S. Effect of HIV-2 infection on HIV-1 disease progression – author reply 2–3. N Engl J Med. 2012;367:1961–2.

    Article  PubMed  Google Scholar 

  • de Silva TI, Peng Y, Leligdowicz A, Zaidi I, Li L, Griffin H, Blais ME, Vincent T, Saraiva M, Yindom LM, et al. Correlates of T-cell-mediated viral control and phenotype of CD8(+) T cells in HIV-2, a naturally contained human retroviral infection. Blood. 2013;121:4330–9.

    Article  PubMed  Google Scholar 

  • Dittmer U, Luke W, Stahl-Hennig C, Coulibaly C, Petry H, Bodemer W, Hunsmann G, Voss G. Early helper T-cell dysfunction in simian immunodeficiency virus but not in human immunodeficiency virus type-2-infected macaques. J Med Primatol. 1994;23:298–303.

    Article  CAS  PubMed  Google Scholar 

  • Duvall MG, Jaye A, Dong T, Brenchley JM, Alabi AS, Jeffries DJ, van der Sande M, Togun TO, McConkey SJ, Douek DC, et al. Maintenance of HIV-specific CD4+ T cell help distinguishes HIV-2 from HIV-1 infection. J Immunol. 2006;176:6973–81.

    Article  CAS  PubMed  Google Scholar 

  • Duvall MG, Lore K, Blaak H, Ambrozak DA, Adams WC, Santos K, Geldmacher C, Mascola JR, McMichael AJ, Jaye A, et al. Dendritic cells are less susceptible to human immunodeficiency virus type 2 (HIV-2) infection than to HIV-1 infection. J Virol. 2007;81:13486–98.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Duvall MG, Precopio ML, Ambrozak DA, Jaye A, McMichael AJ, Whittle HC, Roederer M, Rowland-Jones SL, Koup RA. Polyfunctional T cell responses are a hallmark of HIV-2 infection. Eur J Immunol. 2008;38:350–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Esbjornsson J, Mansson F, Kvist A, Isberg PE, Nowroozalizadeh S, Biague AJ, da Silva ZJ, Jansson M, Fenyo EM, Norrgren H, et al. Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection. N Engl J Med. 2012;367:224–32.

    Article  PubMed  Google Scholar 

  • Gillespie GM, Pinheiro S, Sayeid-Al-Jamee M, Alabi A, Kaye S, Sabally S, Sarge-Njie R, Njai H, Joof K, Jaye A, 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. 2005;35:1445–53.

    Article  CAS  PubMed  Google Scholar 

  • Gotch FM, Nixon DF, Alp N, McMichael AJ, Boryslewicz LK. High frequency of memory and effector gag specific cytotoxic T lymphocytes in HIV seropositive individuals. Int Immunol. 1990;2:707–12.

    Article  CAS  PubMed  Google Scholar 

  • Gotch F, McAdam SN, Allsopp CE, Gallimore A, Elvin J, Kieny MP, Hill AV, McMichael AJ, Whittle HC. Cytotoxic T cells in HIV2 seropositive Gambians. Identification of a virus-specific MHC-restricted peptide epitope. J Immunol. 1993;151:3361–9.

    CAS  PubMed  Google Scholar 

  • Greenberg AE. Possible protective effect of HIV-2 against incident HIV-1 infection: review of available epidemiological and in vitro data. AIDS. 2001;15:2319–21.

    Article  CAS  PubMed  Google Scholar 

  • Hamel DJ, Sankale JL, Eisen G, Meloni ST, Mullins C, Gueye-Ndiaye A, Mboup S, Kanki PJ. Twenty years of prospective molecular epidemiology in Senegal: changes in HIV diversity. AIDS Res Hum Retroviruses. 2007;23:1189–96.

    Article  CAS  PubMed  Google Scholar 

  • Hansmann A, van der Loeff MFS, Kaye S, Awasana AA, Sarge-Njie R, O’Donovan D, Ariyoshi K, Alabi A, Milligan P, Whittle HC. 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. 2005;38:335–41.

    PubMed  Google Scholar 

  • Jaye A, Sarge-Njie R, van der Loeff MS, Todd J, Alabi A, Sabally S, Corrah T, Whittle H. No differences in cellular immune responses between asymptomatic HIV type 1– and type 2–infected Gambian patients. J Infect Dis. 2004;189:498–505.

    Article  PubMed  Google Scholar 

  • Jennes W, Camara M, Dièye T, Mboup S, Kestens L. Higher homologous and lower cross-reactive gag-specific T-cell responses in human immunodeficiency virus type 2 (HIV-2) than in HIV-1 infection. J Virol. 2008;82:8619–28.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Koblavi-Deme S, Kestens L, Hanson D, Otten RA, Borget MY, Bile C, Wiktor SZ, Roels TH, Chorba T, Nkengasong JN. Differences in HIV-2 plasma viral load and immune activation in HIV-1 and HIV-2 dually infected persons and those infected with HIV-2 only in Abidjan, Cote D’Ivoire. AIDS. 2004;18:413–9.

    Article  PubMed  Google Scholar 

  • Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, Farthing C, Ho DD. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol. 1994;68:4650–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Laguette N, Sobhian B, Casartelli N, Ringeard M, Chable-Bessia C, Segeral E, Yatim A, Emiliani S, Schwartz O, Benkirane M. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature. 2011;474:654–U132.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leligdowicz A, Yindom LM, Onyango C, Sarge-Njie R, Alabi A, Cotten M, Vincent T, da Costa C, Aaby P, Jaye A, et al. Robust gag-specific T cell responses characterize viremia control in HIV-2 infection. J Clin Invest. 2007;117:3067–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leligdowicz A, Onyango C, Yindom LM, Peng Y, Cotten M, Jaye A, McMichael A, Whittle H, Dong T, Rowland-Jones S. Highly avid, oligoclonal, early-differentiated antigen-specific CD8+ T cells in chronic HIV-2 infection. Eur J Immunol. 2010;40:1963–72.

    Article  CAS  PubMed  Google Scholar 

  • Lopes AR, Jaye A, Dorrell L, Sabally S, Alabi A, Jones NA, Flower DR, De Groot A, Newton P, Lascar RM, et al. Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection. J Immunol. 2003;171:307–16.

    Article  CAS  PubMed  Google Scholar 

  • Manel N, Hogstad B, Wang Y, Levy DE, Unutmaz D, Littman DR. A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature. 2010;467:214–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mansson F, Biague A, da Silva ZJ, Dias F, Nilsson LA, Andersson S, Fenyo EM, Norrgren H. Prevalence and incidence of HIV-1 and HIV-2 before, during and after a civil war in an occupational cohort in Guinea-Bissau, West Africa. AIDS. 2009;23:1575–82.

    Article  PubMed  Google Scholar 

  • Marlink R, Kanki P, Thior I, Travers K, Eisen G, Siby T, Traore I, Hsieh C, Dia M, Gueye E, et al. Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science. 1994;265:1587–90.

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Steele E, Awasana AA, Corrah T, Sabally S, van der Sande M, Jaye A, Togun T, Sarge-Njie R, McConkey SJ, Whittle H, et al. Is HIV-2- induced AIDS different from HIV-1-associated AIDS? Data from a West African clinic. AIDS. 2007;21:317–24.

    Article  PubMed  Google Scholar 

  • Mothe BR, Horton H, Carter DK, Allen TM, Liebl ME, Skinner P, Vogel TU, Fuenger S, Vielhuber K, Rehrauer W, et al. Dominance of CD8 responses specific for epitopes bound by a single major histocompatibility complex class I molecule during the acute phase of viral infection. J Virol. 2002;76:875–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mulder DW, Nunn AJ, Kamali A, Nakiyingi J, Wagner HU, Kengeyakayondo JF. 2-year HIV-1-associated mortality in a Ugandan rural-population. Lancet. 1994;343:1021–3.

    Article  CAS  PubMed  Google Scholar 

  • Navis M, Schellens I, van Baarle D, Borghans J, van Swieten P, Miedema F, Kootstra N, Schuitemaker H. Viral replication capacity as a correlate of HLA B57/B5801-associated nonprogressive HIV-1 infection. J Immunol. 2007;179:3133–43.

    Article  CAS  PubMed  Google Scholar 

  • Norrgren H, Andersson S, Biague AJ, da Silva ZJ, Dias F, Naucler A, Biberfeld G. Trends and interaction of HIV-1 and HIV-2 in Guinea-Bissau, west Africa: no protection of HIV-2 against HIV-1 infection. AIDS. 1999;13:701–7.

    Article  CAS  PubMed  Google Scholar 

  • Pantaleo G, Demarest JF, Schacker T, Vaccarezza M, Cohen OJ, Daucher M, Graziosi C, Schnittman SS, Quinn TC, Shaw GM, et al. The qualitative nature of the primary immune response to HIV infection is a prognosticator of disease progression independent of the initial level of plasma viremia. Proc Natl Acad Sci U S A. 1997;94:254–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Poulsen AG, Aaby P, Larsen O, Jensen H, Nauclér A, Lisse IM, Christiansen CB, Dias F, Melbye M. 9-year HIV-2-associated mortality in an urban community in Bissau, west Africa. Lancet. 1997;349:911–4.

    Google Scholar 

  • Ranasinghe S, Flanders M, Cutler S, Soghoian DZ, Ghebremichael M, Davis I, Lindqvist M, Pereyra F, Walker BD, Heckerman D, et al. HIV-specific CD4 T cell responses to different viral proteins have discordant associations with viral load and clinical outcome. J Virol. 2012;86(1):277–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Raugi DN, Gottlieb GS, Sow PS, Toure M, Sall F, Gaye A, N’Doye I, Kiviat NB, Hawes SE. HIV-1 outcompetes HIV-2 in dually infected Senegalese individuals with low CD4(+) cell counts. AIDS. 2013;27:2441–50.

    Article  PubMed Central  PubMed  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. 2007;8:329–31.

    Article  CAS  PubMed  Google Scholar 

  • Sarr AD, Lu Y, Sankale JL, Eisen G, Popper S, Mboup S, Kanki PJ, Cao H. Robust HIV type 2 cellular immune response measured by a modified anthrax toxin-based enzyme-linked immunospot assay. AIDS Res Hum Retroviruses. 2001;17:1257–64.

    Article  CAS  PubMed  Google Scholar 

  • Thiebaut R, Matheron S, Taieb A, Brun-Vezinet F, Chene G, Autran B. Long-term nonprogressors and elite controllers in the ANRS CO5 HIV-2 cohort. AIDS. 2011;25:865–7.

    Article  PubMed  Google Scholar 

  • Travers K, Mboup S, Marlink R, Gueye-Nidaye A, Siby T, Thior I, Traore I, Dieng-Sarr A, Sankale JL, Mullins C, et al. Natural protection against HIV-1 infection provided by HIV-2. Science. 1995;268:1612–5.

    Article  CAS  PubMed  Google Scholar 

  • van der Loeff MFS, Larke N, Kaye S, Berry N, Ariyoshi K, Alabi A, van Tienen C, Leligdowicz A, Sarge-Njie R, da Silva Z, et al. Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village. Retrovirology. 2010;7:1–10.

    Article  Google Scholar 

  • van Tienen C, Schim van der Loeff M, Peterson I, Cotten M, Andersson S, Holmgren B, Vincent T, de Silva T, Rowland-Jones S, Aaby P, et al. HTLV-1 and HIV-2 infection are associated with increased mortality in a rural West African community. PLoS One. 2011;6, e29026.

    Article  PubMed Central  PubMed  Google Scholar 

  • Voss G, Nick S, Otteken A, Luke W, Stahl-Hennig C, Hunsmann G. Virus-specific cytotoxic T-lymphocytes in HIV-2-infected cynomolgus macaques. AIDS. 1992;6:1077–83.

    Article  CAS  PubMed  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 TRIM5alpha alleles. J Virol. 2005;79:11580–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zheng NN, Kiviat NB, Sow PS, Hawes SE, Wilson A, Diallo-Agne H, Critchlow CW, Gottlieb GS, Musey L, McElrath MJ. Comparison of human immunodeficiency virus (HIV)-specific T-cell responses in HIV-1- and HIV-2-infected individuals in Senegal. J Virol. 2004;78:13934–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zheng NN, McElrath MJ, Sow P-S, Hawes SE, Diallo-Agne H, Stern JE, Li F, Mesher AL, Robinson AD, Gottlieb GS, et al. Role of human immunodeficiency virus (HIV)-specific T-cell immunity in control of dual HIV-1 and HIV-2 infection. J Virol. 2007;81:9061–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nuffield Department of Medicine, University of Oxford, NDM Research Building, Old Road Campus, Roosevelt Drive, Headington, Oxford, Oxfordshire, OX3 7FZ, UK

    Sophie M. Andrews, Glenn Wong & Sarah L. Rowland-Jones

Authors
  1. Sophie M. Andrews
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Glenn Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah L. Rowland-Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah L. Rowland-Jones .

Editor information

Editors and Affiliations

  1. Dept. Cell & Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA

    Thomas J. Hope

  2. Office of Graduate and Postdoctoral Studies, University of Miami, Miller School of Medicine, Miami, Florida, USA

    Mario Stevenson

  3. University of California, San Diego Dept. Pathology, La Jolla, California, USA

    Douglas Richman

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this entry

Cite this entry

Andrews, S.M., Wong, G., Rowland-Jones, S.L. (2015). The Cellular Immune Response to HIV-2 Infection. In: Hope, T., Stevenson, M., Richman, D. (eds) Encyclopedia of AIDS. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9610-6_38-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-9610-6_38-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-9610-6

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation