共 27 条
Infrequent Recovery of HIV from but Robust Exogenous Infection of Activated CD4+ T Cells in HIV Elite Controllers
被引:91
作者:

Julg, B.
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机构:
Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
Harvard Univ, Boston, MA 02115 USA Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

Pereyra, F.
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机构:
Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
Harvard Univ, Boston, MA 02115 USA Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

Buzon, M. J.
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机构:
Hosp Badalona Germans Trias & Pujol, IrsiCaixa Fdn, Badalona, Spain Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

Piechocka-Trocha, A.
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h-index: 0
机构:
Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
Harvard Univ, Boston, MA 02115 USA
Howard Hughes Med Inst, Chevy Chase, MD USA Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

Clark, M. J.
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Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
Harvard Univ, Boston, MA 02115 USA Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

Baker, B. M.
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Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
Harvard Univ, Boston, MA 02115 USA Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

Lian, J.
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Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
Harvard Univ, Boston, MA 02115 USA Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

Miura, T.
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机构:
Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
Harvard Univ, Boston, MA 02115 USA
Howard Hughes Med Inst, Chevy Chase, MD USA
Univ Tokyo, Inst Med Sci, Tokyo, Japan Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

Martinez-Picado, J.
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h-index: 0
机构:
Hosp Badalona Germans Trias & Pujol, IrsiCaixa Fdn, Badalona, Spain
Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

Addo, M. M.
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h-index: 0
机构:
Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
Harvard Univ, Boston, MA 02115 USA Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

Walker, B. D.
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h-index: 0
机构:
Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
Harvard Univ, Boston, MA 02115 USA
Howard Hughes Med Inst, Chevy Chase, MD USA Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
机构:
[1] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA
[2] Harvard Univ, Boston, MA 02115 USA
[3] Howard Hughes Med Inst, Chevy Chase, MD USA
[4] Hosp Badalona Germans Trias & Pujol, IrsiCaixa Fdn, Badalona, Spain
[5] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain
[6] Univ Tokyo, Inst Med Sci, Tokyo, Japan
基金:
美国国家卫生研究院;
关键词:
HUMAN-IMMUNODEFICIENCY-VIRUS;
ANTIRETROVIRAL THERAPY;
REPLICATION CAPACITY;
VIRAL REPLICATION;
EX-VIVO;
TYPE-1;
LYMPHOCYTES;
SUPPRESSORS;
VIREMIA;
ABSENCE;
D O I:
10.1086/653677
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Background. Human immunodeficiency virus (HIV) elite controllers are able to control infection with HIV-1 spontaneously to undetectable levels in the absence of antiretroviral therapy, but the mechanisms leading to this phenotype are poorly understood. Although low frequencies of HIV-infected peripheral CD4(+) T cells have been reported in this group, it remains unclear to what extent these are due to viral attenuation, active immune containment, or intracellular host factors that restrict virus replication. Methods. We assessed proviral DNA levels, autologous viral growth from and infectability of in vitro activated, CD8(+) T cell-depleted CD4(+) T cells from HIV elite controllers (mean viral load, <50 copies/mL), viremic controllers (mean viral load, <2000 copies/mL), chronic progressors, and individuals receiving highly active antiretroviral therapy. Results. Although we successfully detected autologous virus production in ex vivo activated CD4(+) T cells from all chronic progressors and from most of the viremic controllers, we were able to measure robust autologous viral replication in only 2 of 14 elite controllers subjected to the same protocol. In vitro activated autologous CD4(+) T cells from elite controllers, however, supported infection with both X4 and R5 tropic HIV strains at comparable levels to those in CD4(+) T cells from HIV-uninfected subjects. Proviral DNA levels were the lowest in elite controllers, suggesting that extremely low frequencies of infected cells contribute to difficulty in isolation of virus. Conclusions. These data indicate that elite control is not due to inability of activated CD4(+) T cells to support HIV infection, but the relative contributions of host and viral factors that account for maintenance of low-level infection remain to be determined.
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收藏
页码:233 / 238
页数:6
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Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

Kim, Scott Y.
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Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

Siliciano, Robert F.
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Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

Blankson, Joel N.
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Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[10]
Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities
[J].
Frahm, N
;
Korber, BT
;
Adams, CM
;
Szinger, JJ
;
Draenert, R
;
Addo, MM
;
Feeney, ME
;
Yusim, K
;
Sango, K
;
Brown, NV
;
SenGupta, D
;
Piechocka-Trocha, A
;
Simonis, T
;
Marincola, FM
;
Wurcel, AG
;
Stone, DR
;
Russell, CJ
;
Adolf, P
;
Cohen, D
;
Roach, T
;
StJohn, A
;
Khatri, A
;
Davis, K
;
Mullins, J
;
Goulder, PJR
;
Walker, BD
;
Brander, C
.
JOURNAL OF VIROLOGY,
2004, 78 (05)
:2187-2200

Frahm, N
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Korber, BT
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Adams, CM
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Szinger, JJ
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Draenert, R
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Addo, MM
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Feeney, ME
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Yusim, K
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Sango, K
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Brown, NV
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

SenGupta, D
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Piechocka-Trocha, A
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Simonis, T
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Marincola, FM
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Wurcel, AG
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Stone, DR
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Russell, CJ
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Adolf, P
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Cohen, D
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Roach, T
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StJohn, A
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Khatri, A
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA

Davis, K
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Mullins, J
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Goulder, PJR
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Walker, BD
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Brander, C
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