Comparative Retroviral Epigenomics

摘要 尽管针对hiv的有效抗逆转录病毒疗法(Art)已经开发出来，但即使是治愈方法也仍然难以捉摸。 三十多年后。因为病毒会整合到宿主DNA中，无论有没有，它都能让自己沉默 通过利用宿主表观遗传机制，ART在掩盖其存在方面非常有效 免疫系统，使其难以清除。已经提出了两种试图治愈该病毒的策略 一劳永逸地，两者都依赖于表观遗传调节。第一个提议是通过以下方式“踢死”病毒 逆转沉默修改，以使免疫系统可以看到病毒。第二个战略 建议通过引入永久的表观遗传沉默来阻止和锁定病毒，导致功能上的 临床治愈。这两种策略都需要对表观遗传沉默有更全面的理解。 艾滋病毒前病毒利用的修饰。母公司K01提案试图更具体地描述 两种已知修饰(DNA甲基化和H3K27me3)在慢性粒细胞白血病患者临床样本中的作用 HIV，并将它们与感染SIV的恒河猴进行比较，SIV被认为是最好的动物模型 HIV感染，因为任何和所有表观遗传目标都可能首先在它们身上进行测试。 新冠肺炎疫情阻碍了全球的科学研究，并对新的调查人员产生了严重影响。 最初的K01提案也不例外，因为这笔赠款的主要调查员受到了很大影响 受大流行的影响。因此，本补编力求克服#年大流行带来的障碍。 以完成这项研究大脑中的前驱静默的重要工作。大脑是一个特别重要的 储藏组织，因为已知病毒在这个部位自我隔离，并似乎在发育中发挥作用 艾滋病病毒携带者(PWH)的认知障碍。因此，我们正在评估相同的机制是否 在恒河猴的大脑中扮演着SIV的角色。

Abstract Although effective antiretroviral therapies (ART) have been developed for HIV, a cure has remained elusive even after more than three decades. Because the virus integrates into host DNA and can silence itself with or without ART through harnessing host epigenetic mechanisms, it is highly effective at masking its presence from the immune system, making its clearance difficult. Two strategies have been proposed to attempt to cure the virus once and for all, both dependent upon epigenetic modulation. The first proposes to 'kick and kill' the virus by reversing silencing modifications in order to make the virus visible to the immune system. The second strategy proposes to 'block and lock' the virus by introducing permanent epigenetic silencing, resulting in a functional clinical cure. Both strategies require a far more exhaustive understanding of the epigenetic silencing modifications exploited by the HIV provirus. The parent K01 proposal sought to characterize more specifically the role of two known modifications (DNA methylation and H3K27me3) from clinical samples of patients with HIV, and to compare them to rhesus macaques with SIV, which are considered to be the best animal model for HIV infection, as any and all epigenetic targets will likely be tested on them first. The COVID-19 pandemic hindered scientific research across the globe and impacted new investigators heavily. This original K01 proposal was no exception, as the primary investigator on this grant was substantially impacted by the pandemic. Therefore, this supplement seeks to overcome the barriers introduced by the pandemic in order to finish this important work examining proviral silencing in the brain. The brain is a particularly important reservoir tissue, as the virus is known to sequester itself at this site and appears to play a role in the development of cognitive impairment in people with HIV (PWH). Therefore, we are evaluating whether the same mechanisms are at play for SIV in the brains of rhesus macaques.