Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections
Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections
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DOI：
10.1182/blood-2012-06-437608
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发表时间：
2012-11-15
期刊：
影响因子：
20.3
通讯作者：
Estes, Jacob D.
中科院分区：
文献类型：
--
作者：
Brenchley, Jason M.;Vinton, Carol;Estes, Jacob D.
猴免疫缺陷病毒(SIV)的非人类灵长类自然宿主会发展成无法解决的慢性感染，但不会发展成艾滋病。SIV感染在自然宿主中的非进行性感染的机制尚不清楚，这种感染是维持高水平血浆病毒血症的基础，而没有明显的靶细胞丢失。在这里，我们使用了综合的方法(即FACS分选、定量RT-PCR、免疫组织化学和原位杂交)来研究慢性SIV感染恒河猴(RMS)、HIV感染人类和SIVsmm感染煤眉猴(SM)队列中外周血和淋巴组织(LT)CD4(+)T细胞亚群中的病毒感染。我们发现：(1)在慢性SIV感染的RMS中，CD4(+)T细胞的感染频率显著高于SIVsmm感染的SMS；(2)在SIV感染的RMS和SMS中，感染细胞位于不同的解剖位置和不同的CD4(+)T细胞亚群，RMS的感染模式反映了人类的HIV感染；(3)RMS和人类的TFH细胞感染频率高于SIV感染的SMS；(4)与SMS相比，RMS和人类的LT病毒负荷增加，包括滤泡树突状细胞的病毒沉积。这些数据为自然宿主如何在避免免疫缺陷的同时维持高水平的血浆病毒血症提供了洞察力。(血。2012；120(20)：4172-4181)
Nonhuman primate natural hosts for simian immunodeficiency viruses (SIV) develop a nonresolving chronic infection but do not develop AIDS. Mechanisms to explain the nonprogressive nature of SIV infection in natural hosts that underlie maintained high levels of plasma viremia without apparent loss of target cells remain unclear. Here we used comprehensive approaches (ie, FACS sorting, quantitative RT-PCR, immunohistochemistry, and in situ hybridization) to study viral infection within subsets of peripheral blood and lymphoid tissue (LT) CD4(+) T cells in cohorts of chronically SIV-infected rhesus macaques (RMs), HIV-infected humans, and SIVsmm-infected sooty mangabeys (SMs). We find: (1) infection frequencies among CD4(+) T cells in chronically SIV-infected RMs are significantly higher than those in SIVsmm-infected SMs; (2) infected cells are found in distinct anatomic LT niches and different CD4(+) T-cell subsets in SIV-infected RMs and SMs, with infection patterns of RMs reflecting HIV infection in humans; (3) TFH cells are infected at higher frequencies in RMs and humans than in SMs; and (4) LT viral burden, including follicular dendritic cell deposition of virus, is increased in RMs and humans compared with SMs. These data provide insights into how natural hosts are able to maintain high levels of plasma viremia while avoiding development of immunodeficiency. (Blood. 2012; 120(20): 4172-4181)