CEA, Division of Immuno-Virology, DSV/iMETI, Fontenay-aux-Roses, France.
Retrovirology. 2009 Nov 23;6:106. doi: 10.1186/1742-4690-6-106.
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.
对初次感染的广泛研究对于我们了解 HIV 疾病的进程至关重要。在 SIV 感染的猕猴模型中，我们使用了三种标记物——病毒 RNA、2LTR 环和病毒 DNA——来同时评估初次感染和慢性感染期间血液、次级淋巴组织和肠道中的病毒复制和传播。在感染慢性期，通过细胞分选和三种标记物的病毒定量，评估了病毒在感染外周血中主要靶细胞中的随后的病毒区室化。
在初次感染和早期慢性感染期间，给定组织中病毒 RNA、2LTR 环和 DNA 水平的演变是相关的。血浆病毒载量的下降主要反映了肠道相关淋巴组织（GALT）中病毒复制的大量减少，而脾和外周淋巴结中的病毒 RNA 和 DNA 水平保持稳定。随后，在慢性感染期间，外周血中的中央记忆 CD4+T 细胞逐渐耗竭，伴随着该亚型细胞中高水平的病毒复制。在感染的这个阶段，也发现病毒在幼稚 CD4+T 细胞中复制。病毒 RNA 经常在单核细胞中检测到，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。
我们证明了初次感染和早期慢性感染期间病毒复制和传播的持续存在，主要在次级淋巴组织中。在慢性感染期间，中央记忆 CD4+T 细胞是外周血中病毒复制的主要部位，但病毒也在幼稚 CD4+T 细胞中复制。单核细胞的作用似乎仅限于作为携带病毒的载体，因为观察到这些细胞中没有复制。这些数据对于将 HIV 治疗靶向这些不同的隔室可能具有重要意义。
