Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques.
Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques.
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DOI：
10.1186/1742-4690-6-106
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发表时间：
2009-11-23
期刊：
影响因子：
3.3
通讯作者：
Le Grand R
中科院分区：
文献类型：
--
作者：
Mannioui A;Bourry O;Sellier P;Delache B;Brochard P;Andrieu T;Vaslin B;Karlsson I;Roques P;Le Grand R
对原发感染的广泛研究对我们理解艾滋病毒的病程至关重要。在SIV感染猕猴中，我们使用了三种标记物--病毒RNA、2ltR环和病毒DNA--的组合来评估病毒在原发和慢性感染期间在血液、次级淋巴组织和肠道中的复制和传播。对感染慢性期外周血中病毒的主要靶细胞进行细胞分选和病毒定量，并对三种标志物进行检测，以评价病毒在慢性期的区划。病毒RNA、2ltR环和DNA水平在初发和早期慢性感染期间在特定组织中的演变是相关的。血浆病毒载量的下降主要反映了肠道相关淋巴组织(GALT)中病毒复制的大幅下降，而脾和外周淋巴结中的病毒RNA和DNA水平保持稳定。后来，在慢性感染期间，观察到外周血中的中央记忆CD4+T细胞逐渐耗尽，并伴随着这一亚型细胞中高水平的病毒复制。在感染的这一点上，病毒也被发现在幼稚的CD4+T细胞中复制。在单核细胞中经常检测到病毒RNA，但在这些细胞中似乎没有SIV复制，因为没有检测到病毒DNA或2ltr环。在原发和早期慢性感染期间，我们证明了病毒复制和传播的持久性，主要是在次级淋巴组织中。在慢性感染期间，外周血中病毒复制的主要部位是中枢记忆的CD4+T细胞，但初始的CD4+T细胞中也有病毒复制。单核细胞的作用似乎仅限于携带病毒作为货物，因为观察到这些细胞缺乏复制。这些数据可能对针对这些不同分区的艾滋病毒治疗具有重要影响。
Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT), with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important implications for the targeting of HIV treatment to these diverse compartments.
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影响因子：
3.7
作者：
Kilzer, JM;Stracker, T;Bushman, FD
通讯作者：
Bushman, FD
影响因子：
3.8
作者：
Bourry, Olivier;Brochard, Patricia;Le Grand, Roger
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Le Grand, Roger
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Katzenstein, TL;Pedersen, C;Gerstoft, J
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Gerstoft, J
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作者：
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3.8
作者：
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