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Figure 2: Changes in CD4+ T cell numbers as a function of viral replication and dissemination in the peripheral blood, in four groups of SIV-infected macaques during primary infection. (A) Protocol for SIV infection, evaluations, and the euthanasia of each animal. Each box indicates the group of macaques explored at the corresponding times. (B) Changes in absolute counts of total CD4+ T cells in peripheral blood. (C-D-E) Changes in viral RNA levels in plasma and viral DNA and 2LTR circle levels in PBMCs. Bold lines indicate the mean value (B-D-C-E).

Image Text (High Precision): 100 2-LTR 2000 2LTR 50 CD4 DNA PBMCs Plasma RNA SIVmac251 Total cells circulating copies days groups infecte infected infection levels load lymphocytes macaques viral

Other Images from "Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques":


Figure 5 Correlation between plasma viral load an...

Figure 7 Changes in immunological parameters and ...

Figure 2 Changes in CD4+ T cell numbers as a func...

Figure 6 Flow cytometric sorting strategy for mon...

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Figure 1 The dynamics of CD4+ T cells, viral repl...

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Abstract

BackgroundExtensive 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.ResultsThe 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.ConclusionWe 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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