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. [1 ,2 ]
Pereyra, F. [1 ,2 ]
Buzon, M. J. [4 ]
Piechocka-Trocha, A. [1 ,2 ,3 ]
Clark, M. J. [1 ,2 ]
Baker, B. M. [1 ,2 ]
Lian, J. [1 ,2 ]
Miura, T. [1 ,2 ,3 ,6 ]
Martinez-Picado, J. [4 ,5 ]
Addo, M. M. [1 ,2 ]
Walker, B. D. [1 ,2 ,3 ]
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.
引用
收藏
页码:233 / 238
页数:6
相关论文
共 27 条
[1]   Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection [J].
Alexander, L ;
Weiskopf, E ;
Greenough, TC ;
Gaddis, NC ;
Auerbach, MR ;
Malim, MH ;
O'Brien, SJ ;
Walker, BD ;
Sullivan, JL ;
Desrosiers, RC .
JOURNAL OF VIROLOGY, 2000, 74 (09) :4361-4376
[2]   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
[3]   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
[4]   Analysis of early human immunodeficiency virus type 1 DNA synthesis by use of a new sensitive assay for quantifying integrated provirus [J].
Brussel, A ;
Sonigo, P .
JOURNAL OF VIROLOGY, 2003, 77 (18) :10119-10124
[5]   VIROLOGICAL AND IMMUNOLOGICAL CHARACTERIZATION OF LONG-TERM SURVIVORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION [J].
CAO, YZ ;
QIN, LM ;
ZHANG, LQ ;
SAFRIT, J ;
HO, DD .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (04) :201-208
[6]   Differential Neutralization of Human Immunodeficiency Virus (HIV) Replication in Autologous CD4 T Cells by HIV-Specific Cytotoxic T Lymphocytes [J].
Chen, Huabiao ;
Piechocka-Trocha, Alicja ;
Miura, Toshiyuki ;
Brockman, Mark A. ;
Julg, Boris D. ;
Baker, Brett M. ;
Rothchild, Alissa C. ;
Block, Brian L. ;
Schneidewind, Arne ;
Koibuchi, Tomohiko ;
Pereyra, Florencia ;
Allen, Todd M. ;
Walker, Bruce D. .
JOURNAL OF VIROLOGY, 2009, 83 (07) :3138-3149
[7]   GENOMIC STRUCTURE OF AN ATTENUATED QUASI-SPECIES OF HIV-1 FROM A BLOOD-TRANSFUSION DONOR AND RECIPIENTS [J].
DEACON, NJ ;
TSYKIN, A ;
SOLOMON, A ;
SMITH, K ;
LUDFORDMENTING, M ;
HOOKER, DJ ;
MCPHEE, DA ;
GREENWAY, AL ;
ELLETT, A ;
CHATFIELD, C ;
LAWSON, VA ;
CROWE, S ;
MAERZ, A ;
SONZA, S ;
LEARMONT, J ;
SULLIVAN, JS ;
CUNNINGHAM, A ;
DWYER, D ;
DOWTON, D ;
MILLS, J .
SCIENCE, 1995, 270 (5238) :988-991
[8]   Human immunodeficiency virus controllers: Mechanisms of durable virus control in the absence of antiretroviral therapy [J].
Deeks, Steven G. ;
Walker, Bruce D. .
IMMUNITY, 2007, 27 (03) :406-416
[9]   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
[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