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.
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页数:12
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共 59 条
[1]   The CXCR4-Tropic Human Immunodeficiency Virus Envelope Promotes More-Efficient Gene Delivery to Resting CD4+ T Cells than the Vesicular Stomatitis Virus Glycoprotein G Envelope [J].
Agosto, Luis M. ;
Yu, Jianqing J. ;
Liszewski, Megan K. ;
Baytop, Clifford ;
Korokhov, Nikolay ;
Humeau, Laurent M. ;
O'Doherty, Una .
JOURNAL OF VIROLOGY, 2009, 83 (16) :8153-8162
[2]   Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover [J].
Almeida, Jorge R. ;
Price, David A. ;
Papagno, Laura ;
Arkoub, Zaina Ait ;
Sauce, Delphine ;
Bornstein, Ethan ;
Asher, Tedi E. ;
Samri, Assia ;
Schnuriger, Aurelie ;
Theodorou, Ioannis ;
Costagliola, Dominique ;
Rouzioux, Christine ;
Agut, Henri ;
Marcelin, Anne-Genevieve ;
Douek, Daniel ;
Autran, Brigitte ;
Appay, Victor .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (10) :2473-2485
[3]   Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection [J].
Altfeld, M ;
Addo, MA ;
Rosenberg, ES ;
Hecht, FA ;
Lee, PK ;
Vogel, M ;
Yu, XG ;
Draenert, R ;
Johnston, MN ;
Strick, D ;
Allen, TA ;
Feeney, ME ;
Kahn, JO ;
Sekaly, RP ;
Levy, JA ;
Rockstroh, JK ;
Goulder, PJR ;
Walker, BD .
AIDS, 2003, 17 (18) :2581-2591
[4]   Maintenance of viral suppression in HIV-1-infected HLA-B*57+ elite suppressors despite CTL escape mutations [J].
Bailey, Justin R. ;
Williams, Thomas M. ;
Siliciano, Robert F. ;
Blankson, Joel N. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (05) :1357-1369
[5]   Evidence of CD8+ T-Cell-Mediated Selective Pressure on Human Immunodeficiency Virus Type 1 nef in HLA-B*57+ Elite Suppressors [J].
Bailey, Justin R. ;
Brennan, Timothy P. ;
O'Connell, Karen A. ;
Siliciano, Robert F. ;
Blankson, Joel N. .
JOURNAL OF VIROLOGY, 2009, 83 (01) :88-97
[6]   HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells [J].
Betts, Michael R. ;
Nason, Martha C. ;
West, Sadie M. ;
De Rosa, Stephen C. ;
Migueles, Stephen A. ;
Abraham, Jonathan ;
Lederman, Michael M. ;
Benito, Jose M. ;
Goepfert, Paul A. ;
Connors, Mark ;
Roederer, Mario ;
Koup, Richard A. .
BLOOD, 2006, 107 (12) :4781-4789
[7]   The study of elite controllers: a pure academic exercise or a potential pathway to an HIV-1 vaccine? [J].
Blankson, Joel .
CURRENT OPINION IN HIV AND AIDS, 2011, 6 (03) :147-150
[8]   Isolation and characterization of replication-competent human immunodeficiency virus type 1 from a subset of elite suppressors [J].
Blankson, Joel N. ;
Bailey, Justin R. ;
Thayil, Seema ;
Yang, Hung-Chih ;
Lassen, Kara ;
Lai, Jun ;
Gandhi, Shiv K. ;
Siliciano, Janet D. ;
Williams, Thomas M. ;
Siliciano, Robert F. .
JOURNAL OF VIROLOGY, 2007, 81 (05) :2508-2518
[9]   Escape and compensation from early HLA-B57-Mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A [J].
Brockman, Mark A. ;
Schneidewind, Arne ;
Lahaie, Matthew ;
Schmidt, Aaron ;
Miura, Toshiyuki ;
DeSouza, Ivna ;
Ryvkin, Faina ;
Derdeyn, Cynthia A. ;
Allen, Susan ;
Hunter, Eric ;
Mulenga, Joseph ;
Goepfert, Paul A. ;
Walker, Bruce D. ;
Allen, Todd M. .
JOURNAL OF VIROLOGY, 2007, 81 (22) :12608-12618
[10]   Inhibitory Potential of Subpopulations of CD8+ T Cells in HIV-1-Infected Elite Suppressors [J].
Buckheit, Robert W., III ;
Salgado, Maria ;
Silciano, Robert F. ;
Blankson, Joel N. .
JOURNAL OF VIROLOGY, 2012, 86 (24) :13679-13688