Mullins James I, Frenkel Lisa M
Departments of Microbiology, Medicine, Global Health and Laboratory Medicine, University of Washington, Seattle, WA, US.
Departments of Pediatrics, Medicine, Global Health and Laboratory Medicine, University of Washington, Seattle, WA, US.
J Infect Dis. 2017 Mar 15;215(suppl_3):S119-S127. doi: 10.1093/infdis/jiw636.
The latent HIV-1 reservoir in blood decays very slowly, even during prolonged suppression of viral replication by antiretroviral therapy (ART). Mechanisms for reservoir persistence include replenishment through low-level viral replication, longevity and homeostatic proliferation of memory T cells, and most recently appreciated, clonal expansion of HIV-infected cells. Clonally expanded cells make up a large and increasing fraction of the residual infected cell population on ART, and insertion of HIV proviruses into certain host cellular genes has been associated with this proliferation. That the vast majority of proviruses are defective clouds our assessment of the degree to which clonally expanded cells harbor infectious viruses, and thus the extent to which they contribute to reservoirs relevant to curing infection. This review summarizes past studies that have defined our current understanding and the gaps in our knowledge of the mechanisms by which proviral integration and clonal expansion sustain the HIV reservoir.
血液中潜伏的HIV-1储存库衰减非常缓慢，即使在通过抗逆转录病毒疗法（ART）长期抑制病毒复制期间也是如此。储存库持续存在的机制包括通过低水平病毒复制进行补充、记忆T细胞的长寿和稳态增殖，以及最近认识到的HIV感染细胞的克隆扩增。克隆扩增细胞在接受ART治疗的残余感染细胞群体中所占比例很大且不断增加，HIV前病毒插入某些宿主细胞基因与这种增殖有关。绝大多数前病毒存在缺陷，这使我们难以评估克隆扩增细胞携带传染性病毒的程度，进而难以评估它们对与治愈感染相关的储存库的贡献程度。本综述总结了过去的研究，这些研究界定了我们目前对前病毒整合和克隆扩增维持HIV储存库机制的理解以及知识空白。
