Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Kunming National High-Level Biosafety Research Center for Nonhuman Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
AIDS Res Hum Retroviruses. 2024 Sep;40(9):521-530. doi: 10.1089/AID.2023.0130. Epub 2024 Apr 12.
HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Because of the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site are also complex. Recently, although a variety of molecules have been reported to be 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 with character of the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 days after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate 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 nonlymphoid 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 nonlymphoid tissues after short-term treatment suggested that the role of nonlymphoid tissues cannot be ignored in development strategies for AIDS therapy.
HIV/AIDS 无法治愈，因为病毒库的持续存在。由于人体器官的细胞组成和结构复杂，解剖部位的 HIV 库也很复杂。最近，虽然有多种分子被报道参与了病毒库的建立和维持，或者作为潜伏细胞的标志物，但研究主要集中在血液和淋巴结上。现在，组织中病毒库的特征还没有完全被理解。在这项研究中，从 SIVmac239 感染的猴子中收集了各种组织，并比较了它们中总 SIV DNA、SIV 2-LTR DNA 和细胞相关病毒 RNA 的水平，以及早期治疗时解剖学病毒库的特征。结果表明，从感染后 3 天开始的短期联合抗逆转录病毒治疗（cART）可以显著抑制病毒血症并减少解剖学病毒库的大小，但不能根除感染和病毒的持续复制。此外，早期 cART 对不同组织中总 SIV DNA、SIV 2-LTR DNA 和细胞相关病毒 RNA 水平的影响不同，这改变了解剖部位病毒库的大小分布。最后，治疗后非淋巴组织，特别是肝脏和肺，对病毒库的贡献增加，而肠道淋巴组织对病毒库的贡献显著减少。这些结果表明，早期治疗有效地减少了病毒库的大小，cART 对组织病毒库的影响因组织类型而异。这些结果表明，病毒在短期治疗后在非淋巴组织中的持续存在表明，非淋巴组织在艾滋病治疗的发展策略中不容忽视。
