Affiliation:
1. Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106;
Abstract
Although potent combination antiretroviral therapy can effectively block viral replication in the host, human immunodeficiency virus (HIV) persists due to the existence of latent but replication-competent proviruses residing primarily in a very small population of resting memory CD4+ T cells. Viral latency is established when the expression of the autoregulatory viral trans-activating factor Tat is reduced to subthreshold levels. The absence of Tat reduces HIV transcription and protein production to levels that make the host cell invisible to the immune system and refractory to antiretroviral treatment. Key host cell mechanisms that drive HIV into latency are sequestration of transcription initiation factors, establishment of epigenetic barriers inactivating the proviral promoter, and blockage of the assembly of the host elongation factor P-TEFb. This comprehensive understanding of the molecular control of HIV transcription is leading to the development of optimized combinatorial reactivation and immune surveillance strategies designed to purge the latent viral reservoir.
Cited by
135 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献