Division of Medical Virology, Stellenbosch University and NHLS Tygerberg, Cape Town, South Africa.
HIV Dynamic and Replication Program, Center for Cancer Research, National Cancer Institute at Frederick, 1050 Boyles Street, Building 535, Room 109, Frederick, MD, 21702-1201, USA.
Retrovirology. 2018 Jan 30;15(1):14. doi: 10.1186/s12977-018-0395-4.
Characterizing HIV genetic diversity and evolution during antiretroviral therapy (ART) provides insights into the mechanisms that maintain the viral reservoir during ART. This review describes common methods used to obtain and analyze intra-patient HIV sequence data, the accumulation of diversity prior to ART and how it is affected by suppressive ART, the debate on viral replication and evolution in the presence of ART, HIV compartmentalization across various tissues, and mechanisms for the emergence of drug resistance. It also describes how CD4+ T cells that were likely infected with latent proviruses prior to initiating treatment can proliferate before and during ART, providing a renewable source of infected cells despite therapy. Some expanded cell clones carry intact and replication-competent proviruses with a small fraction of the clonal siblings being transcriptionally active and a source for residual viremia on ART. Such cells may also be the source for viral rebound after interrupting ART. The identical viral sequences observed for many years in both the plasma and infected cells of patients on long-term ART are likely due to the proliferation of infected cells both prior to and during treatment. Studies on HIV diversity may reveal targets that can be exploited in efforts to eradicate or control the infection without ART.
描述在抗逆转录病毒疗法 (ART) 期间 HIV 遗传多样性和进化的特征，提供了在 ART 期间维持病毒储存库的机制的见解。这篇综述描述了用于获得和分析患者内 HIV 序列数据的常见方法、ART 前多样性的积累以及它如何受到抑制性 ART 的影响、ART 存在下病毒复制和进化的争论、各种组织中 HIV 的分隔化以及耐药性出现的机制。它还描述了在开始治疗之前可能已经被潜伏前病毒感染的 CD4+ T 细胞如何在 ART 之前和期间增殖，尽管进行了治疗，但仍为受感染的细胞提供了可再生的来源。一些扩展的细胞克隆携带完整且具有复制能力的前病毒，其中一小部分克隆的兄弟姐妹具有转录活性，是 ART 时残留病毒血症的来源。这些细胞也可能是中断 ART 后病毒反弹的来源。在长期接受 ART 的患者的血浆和受感染细胞中观察到多年的相同病毒序列可能是由于在治疗之前和期间感染细胞的增殖所致。对 HIV 多样性的研究可能会揭示可以在不使用 ART 的情况下根除或控制感染的目标。
