Primary CD8+ T cells from elite suppressors effectively eliminate non-productively HIV-1 infected resting and activated CD4+ T cells

被引:36
作者
Buckheit, Robert W., III [1 ]
Siliciano, Robert F. [1 ,2 ]
Blankson, Joel N. [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA
来源
RETROVIROLOGY | 2013年 / 10卷
关键词
HIV-1; Latency; Elite Suppression; CD8; Elimination; Non-productive Infection; HUMAN-IMMUNODEFICIENCY-VIRUS; LOW-LEVEL VIREMIA; HIV CONTROLLERS; HLA-C; INFECTED-CELLS; REPLICATION; ASSOCIATION; TYPE-1; GAG; RESPONSES;
D O I
10.1186/1742-4690-10-68
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Background: Elite controllers or suppressors have the remarkable capacity to maintain HIV-1 plasma RNA levels below the limit of detection of clinical assays (<50 copies/mL) without therapy and have a lower frequency of latently infected cells compared to chronic progressors. While it is unclear how this reduced seeding of the reservoir is achieved, it is possible that effective CTL responses play an in important role in limiting the size of the latent reservoir. Results: Herein, we demonstrate that primary CD8(+) T cells from HLA-B*57/5801 elite suppressors were able to efficiently eliminate resting and activated primary CD4(+) T cells shortly after viral entry and prior to productive infection. CD8(+) T cells from elite suppressors were significantly more effective at eliminating these cells than CD8(+) T cells from chronic progressors. Conclusions: Nonproductively infected CD4(+) T cells may represent a subpopulation of cells that are precursors to latently infected cells; therefore, the effective elimination of these cells may partially explain why elite suppressors have a much lower frequency of latently infected cells compared to chronic progressors. Thus, a vaccine strategy that elicits early and potent CD8(+) T cell responses may have the capacity to limit the seeding of the latent reservoir in HIV-1 infection.
引用
收藏
页数:12
相关论文
共 59 条
[11]   MHC-I-restricted presentation of HIV-1 virion antigens without viral replication [J].
Buseyne, F ;
Le Gall, S ;
Boccaccio, C ;
Abastado, JP ;
Lifson, JD ;
Arthur, LO ;
Rivière, Y ;
Heard, JM ;
Schwartz, O .
NATURE MEDICINE, 2001, 7 (03) :344-349
[12]   HIV-1 Disease-Influencing Effects Associated with ZNRD1, HCP5 and HLA-C Alleles Are Attributable Mainly to Either HLA-A10 or HLA-B*57 Alleles [J].
Catano, Gabriel ;
Kulkarni, Hemant ;
He, Weijing ;
Marconi, Vincent C. ;
Agan, Brian K. ;
Landrum, Michael ;
Anderson, Stephanie ;
Delmar, Judith ;
Telles, Vanessa ;
Song, Li ;
Castiblanco, John ;
Clark, Robert A. ;
Dolan, Matthew J. ;
Ahuja, Sunil K. .
PLOS ONE, 2008, 3 (11)
[13]   Distinct Genetic Loci Control Plasma HIV-RNA and Cellular HIV-DNA Levels in HIV-1 Infection: The ANRS Genome Wide Association 01 Study [J].
Dalmasso, Cyril ;
Carpentier, Wassila ;
Meyer, Laurence ;
Rouzioux, Christine ;
Goujard, Cecile ;
Chaix, Marie-Laure ;
Lambotte, Olivier ;
Avettand-Fenoel, Veronique ;
Le Clerc, Sigrid ;
de Senneville, Laure Denis ;
Deveau, Christiane ;
Boufassa, Faroudy ;
Debre, Patrice ;
Delfraissy, Jean-Francois ;
Broet, Philippe ;
Theodorou, Ioannis .
PLOS ONE, 2008, 3 (12)
[14]   A comparison of viral loads between HIV-1-infected elite suppressors and individuals who receive suppressive highly active antiretroviral therapy [J].
Dinoso, Jason B. ;
Kim, Scott Y. ;
Siliciano, Robert F. ;
Blankson, Joel N. .
CLINICAL INFECTIOUS DISEASES, 2008, 47 (01) :102-104
[15]   HLA class I-restricted T-cell responses may contribute to the control of human immunodeficiency virus infection, but such responses are not always necessary for long-term virus control [J].
Emu, Brinda ;
Sinclair, Elizabeth ;
Hatano, Hiroyu ;
Ferre, April ;
Shacklett, Barbara ;
Martin, Jeffrey N. ;
McCune, J. M. ;
Decks, Steven G. .
JOURNAL OF VIROLOGY, 2008, 82 (11) :5398-5407
[16]   A whole-genome association study of major determinants for host control of HIV-1 [J].
Fellay, Jacques ;
Shianna, Kevin V. ;
Ge, Dongliang ;
Colombo, Sara ;
Ledergerber, Bruno ;
Weale, Mike ;
Zhang, Kunlin ;
Gumbs, Curtis ;
Castagna, Antonella ;
Cossarizza, Andrea ;
Cozzi-Lepri, Alessandro ;
De Luca, Andrea ;
Easterbrook, Philippa ;
Francioli, Patrick ;
Mallal, Simon ;
Martinez-Picado, Javier ;
Miro, Jose M. ;
Obel, Niels ;
Smith, Jason P. ;
Wyniger, Josiane ;
Descombes, Patrick ;
Antonarakis, Stylianos E. ;
Letvin, Norman L. ;
McMichael, Andrew J. ;
Haynes, Barton F. ;
Telenti, Amalio ;
Goldstein, David B. .
SCIENCE, 2007, 317 (5840) :944-947
[17]   Mucosal immune responses to HIV-1 in elite controllers: a potential correlate of immune control [J].
Ferre, April L. ;
Hunt, Peter W. ;
Critchfield, J. William ;
Young, Delandy H. ;
Morris, Megan M. ;
Garcia, Juan C. ;
Pollard, Richard B. ;
Yee, Hal F., Jr. ;
Martin, Jeffrey N. ;
Deeks, Steven G. ;
Shacklett, Barbara L. .
BLOOD, 2009, 113 (17) :3978-3989
[18]   Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication [J].
Friedrich, Thomas C. ;
Valentine, Laura E. ;
Yant, Levi J. ;
Rakasz, Eva G. ;
Piaskowski, Shari M. ;
Furlott, Jessica R. ;
Weisgrau, Kimberly L. ;
Burwitz, Benjamin ;
May, Gemma E. ;
Leon, Enrique J. ;
Soma, Taeko ;
Napoe, Gnankang ;
Capuano, Saverio V., III ;
Wilson, Nancy A. ;
Watkins, David I. .
JOURNAL OF VIROLOGY, 2007, 81 (07) :3465-3476
[19]   SERINE PHOSPHORYLATION-INDEPENDENT DOWN-REGULATION OF CELL-SURFACE CD4 BY NEF [J].
GARCIA, JV ;
MILLER, AD .
NATURE, 1991, 350 (6318) :508-511
[20]   Spontaneous Control of Viral Replication during Primary HIV Infection: When Is "HIV Controller" Status Established? [J].
Goujard, Cecile ;
Chaix, Marie-Laure ;
Lambotte, Olivier ;
Deveau, Christiane ;
Sinet, Martine ;
Guergnon, Julien ;
Courgnaud, Valerie ;
Rouzioux, Christine ;
Delfraissy, Jean-Francois ;
Venet, Alain ;
Meyer, Laurence .
CLINICAL INFECTIOUS DISEASES, 2009, 49 (06) :982-986