Verdikt Roxane, Hernalsteens Olivier, Van Lint Carine
Service of Molecular Virology, Department of Molecular Virology (DBM), Université Libre de Bruxelles (ULB), 6041 Gosselies, Belgium.
Vaccines (Basel). 2021 May 17;9(5):514. doi: 10.3390/vaccines9050514.
Eradicating HIV-1 in infected individuals will not be possible without addressing the persistence of the virus in its multiple reservoirs. In this context, the molecular characterization of HIV-1 persistence is key for the development of rationalized therapeutic interventions. HIV-1 gene expression relies on the redundant and cooperative recruitment of cellular epigenetic machineries to -regulatory proviral regions. Furthermore, the complex repertoire of HIV-1 repression mechanisms varies depending on the nature of the viral reservoir, although, so far, few studies have addressed the specific regulatory mechanisms of HIV-1 persistence in other reservoirs than the well-studied latently infected CD4 T cells. Here, we present an exhaustive and updated picture of the heterochromatinization of the HIV-1 promoter in its different reservoirs. We highlight the complexity, heterogeneity and dynamics of the epigenetic mechanisms of HIV-1 persistence, while discussing the importance of further understanding HIV-1 gene regulation for the rational design of novel HIV-1 cure strategies.
如果不解决病毒在其多个储存库中的持续存在问题，就不可能在受感染个体中根除HIV-1。在这种情况下，HIV-1持续存在的分子特征对于合理治疗干预措施的开发至关重要。HIV-1基因表达依赖于细胞表观遗传机制向调节性原病毒区域的冗余和协同募集。此外，HIV-1抑制机制的复杂组成因病毒储存库的性质而异，尽管到目前为止，很少有研究探讨除了经过充分研究的潜伏感染CD4 T细胞之外的其他储存库中HIV-1持续存在的具体调节机制。在这里，我们展示了HIV-1启动子在其不同储存库中的异染色质化的详尽且最新的情况。我们强调了HIV-1持续存在的表观遗传机制的复杂性、异质性和动态性，同时讨论了进一步了解HIV-1基因调控对于合理设计新型HIV-1治愈策略的重要性。
