Murray Alexandra J, Kwon Kyungyoon J, Farber Donna L, Siliciano Robert F
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032; Department of Surgery, Columbia University Medical Center, New York, NY 10032; and.
J Immunol. 2016 Jul 15;197(2):407-17. doi: 10.4049/jimmunol.1600343.
Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus, ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4(+) T cells. In this review, we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate.
针对HIV-1感染的联合抗逆转录病毒疗法（ART）可将血浆病毒水平降低至临床检测方法的检测限以下。然而，即使通过ART长期抑制病毒复制，治疗中断后病毒血症仍会迅速反弹。因此，ART无法治愈。治愈的主要障碍是静息记忆CD4(+) T细胞中潜伏的HIV-1储存库异常稳定。在本综述中，我们探讨了潜伏储存库异常稳定的原因。其稳定性似乎并非源于新感染事件的补充，而是为免疫记忆提供支持的正常生理过程。驱动受感染细胞克隆扩增的增殖过程尤为重要。最近的证据表明，在一些受感染细胞中，增殖是前病毒整合到与细胞生长相关的宿主基因中的结果。通过靶向潜伏储存库来治愈HIV-1感染的努力可能需要考虑潜伏感染细胞增殖的可能性。
