Infrequent recovery of HIV from but robust exogenous infection of activated CD4(+) T cells in HIV elite controllers.
Infrequent recovery of HIV from but robust exogenous infection of activated CD4(+) T cells in HIV elite controllers.
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DOI：
10.1086/653677
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发表时间：
2010-07-15
期刊：
影响因子：
--
通讯作者：
Walker BD
中科院分区：
文献类型：
--
作者：
Julg B;Pereyra F;Buzón MJ;Piechocka-Trocha A;Clark MJ;Baker BM;Lian J;Miura T;Martinez-Picado J;Addo MM;Walker BD
HIV精英控制者能够在没有抗逆转录病毒治疗的情况下自发地将HIV-1感染控制到不可检测的水平，但导致这种表型的机制知之甚少。尽管在这一组中报告了低频率的HIV感染外周CD 4 + T细胞，但仍不清楚这在多大程度上是由于病毒减毒、主动免疫遏制或限制病毒复制的细胞内宿主因素。在这里，我们评估了来自HIV精英控制者（平均VL<50 cp/ml）、病毒血症控制者（平均VL<2000 cp/ml）、慢性进展者和HAART治疗个体的体外活化的、CD 8 + T细胞耗尽的CD 4 + T细胞的前病毒DNA水平、自体病毒生长和感染性。尽管我们成功地检测到来自所有慢性进展者和大多数病毒血症控制者的离体活化的CD 4 + T细胞中的自体病毒产生，但我们仅能够在经历相同方案的14个精英控制者中的仅2个中测量稳健的自体病毒复制。然而，来自精英控制者的体外活化自体CD 4 + T细胞支持X4和R5嗜性HIV毒株的感染，其水平与来自HIV阴性受试者的CD 4 + T细胞相当。前病毒DNA水平在精英控制者中最低，这表明极低频率的感染细胞导致难以分离病毒。这些数据表明，精英控制不是由于活化的CD 4 + T细胞不能支持HIV感染，但宿主和病毒因素的相对贡献，占维持低水平感染仍有待确定。
HIV elite controllers are able to control HIV-1 infection 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 this is due to viral attenuation, active immune containment, or intracellular host factors that restrict virus replication. Here 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 VL<50cp/ml), viremic controllers (mean VL<2000cp/ml), chronic progressors and HAART treated individuals. Although we successfully detected autologous virus production in ex-vivo activated CD4+ T-cells from all chronic progressors and most of the viremic controllers we were only 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 CD4+ T-cells from HIV negative subjects. Proviral DNA levels were the lowest in elite controllers, suggesting that extremely low frequencies of infected cells contributes to difficulty in isolation of virus. These data indicate that elite control is not due to inability of activated CD4+ T-cells to support HIV infection, but the relative contribution of host and viral factors that account for maintenance of low level infection remain to be determined.
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影响因子：
5.4
作者：
Miura, Toshiyuki;Brockman, Mark A.;Walker, Bruce D.
通讯作者：
Walker, Bruce D.
影响因子：
5.4
作者：
Brussel, A;Sonigo, P
通讯作者：
Sonigo, P
DOI：
10.1086/605446
发表时间：
2009-09-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Pereyra F;Palmer S;Miura T;Block BL;Wiegand A;Rothchild AC;Baker B;Rosenberg R;Cutrell E;Seaman MS;Coffin JM;Walker BD
通讯作者：
Walker BD
影响因子：
5.4
作者：
Miura, Toshiyuki;Brockman, Mark A.;Walker, Bruce D.
通讯作者：
Walker, Bruce D.
影响因子：
56.9
作者：
DEACON, NJ;TSYKIN, A;MILLS, J
通讯作者：
MILLS, J