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Nonnegligible contribution of non-lymphoid tissue to viral reservoir during the short-term early cART in SIVmac239-infected Chinese rhesus macaques.

HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Due to the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site is also complex. Recently, although a variety of molecules have been reported to involved in the establishment and maintenance of the viral reservoirs, or as marker of latent cells, the research mainly focuses on blood and lymph nodes. Now, the characteristics of the viral reservoir in tissue are not yet fully understood. In this study, various tissues were collected from SIVmac239 infected monkeys, and the level of total SIV DNA, SIV 2-LTR DNA and cell associated-virus RNA in them were compared to character the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 day after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate de novo infections and ongoing replication of virus. Moreover, the effects of early cART on the level of total SIV DNA, SIV 2-LTR DNA and cell associated-virus RNA in different tissues were different, which changed the size distribution of viral reservoir in anatomical site. Finally, the contribution of non-lymphoid tissues, especially liver and lung, to the viral reservoir increased after treatment, while the contribution of intestinal lymphoid to the viral reservoir significantly reduced. These results suggested that early treatment effectively decreased the size of viral reservoir, and that the effects of cART on the tissue viral reservoir varied greatly by tissue type. The results implied that persistent existence of virus in non-lymphoid tissues after short-term treatment, and suggested that the role of non-lymphoid tissues cannot be ignored in development strategies for AIDS therapy.

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