Christensen-Quick Aaron, Vanpouille Christophe, Lisco Andrea, Gianella Sara
1 University of California San Diego , Center for AIDS Research, La Jolla, California.
2 Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, Maryland.
AIDS Res Hum Retroviruses. 2017 Nov;33(S1):S23-S30. doi: 10.1089/aid.2017.0145.
The inherent stability of a small population of T cells that are latently infected with HIV despite antiretroviral therapy (ART) remains a stubborn obstacle to an HIV cure. By exploiting the memory compartment of our immune system, HIV maintains persistence in a small subset of quiescent cells with varying phenotypes, thus evading immune surveillance and clinical detection. Understanding the molecular and immunological mechanisms that maintain the latent reservoir will be critical to the success of HIV eradication strategies. Human cytomegalovirus (CMV), another chronic viral infection, frequently co-occurs with HIV and occupies an oversized proportion of memory T cell responses. CMV and HIV have both evolved complex strategies to manipulate our immune system for their own advantage. Given the increasingly clear links between CMV replication, chronic immune activation, and increased HIV reservoirs, we present a closer examination of the interplay between these two chronic coinfections. Here we review the effects of CMV on the immune system and show how they may affect persistence of the latent HIV reservoir during ART. The studies described herein suggest that hijacking of cytokine and chemokine signaling, manipulation of cell development pathways, and transactivation of HIV expression by CMV might be pouring gas on the fire of HIV persistence. Future interventional studies are required to formally determine the extent to which CMV is causally associated with inflammation and HIV reservoir expansion.
尽管接受了抗逆转录病毒疗法（ART），一小部分潜伏感染艾滋病毒的T细胞的固有稳定性仍然是治愈艾滋病毒的顽固障碍。通过利用我们免疫系统的记忆区室，艾滋病毒在一小部分具有不同表型的静止细胞中持续存在，从而逃避免疫监视和临床检测。了解维持潜伏库的分子和免疫机制对于艾滋病毒根除策略的成功至关重要。人类巨细胞病毒（CMV），另一种慢性病毒感染，经常与艾滋病毒同时出现，并在记忆T细胞反应中占比过大。CMV和艾滋病毒都进化出了复杂的策略来操纵我们的免疫系统以谋取自身利益。鉴于CMV复制、慢性免疫激活和艾滋病毒库增加之间的联系越来越明显，我们对这两种慢性合并感染之间的相互作用进行了更深入的研究。在这里，我们回顾了CMV对免疫系统的影响，并展示了它们在ART期间可能如何影响潜伏艾滋病毒库的持续存在。本文所述的研究表明，CMV对细胞因子和趋化因子信号的劫持、对细胞发育途径的操纵以及对艾滋病毒表达的反式激活可能会助长艾滋病毒持续存在的火势。未来需要进行干预性研究，以正式确定CMV与炎症和艾滋病毒库扩张之间的因果关系程度。
