ART Modulation of Viral Pathogenesis

描述(申请人提供)：今天，美国大多数感染人类免疫缺陷病毒(HIV)的患者正在接受长期(10年以上)的抗逆转录病毒治疗(ART)。虽然ART可将HIV复制抑制到50拷贝/毫升以下，但这些ART药物对卡波西肉瘤相关疱疹病毒(KSHV)传播和疾病的长期影响知之甚少。我们假设抗逆转录病毒药物暴露直接影响KSHV基因的表达。如果是这样的话，这种机制可能会在病毒Episome的表观遗传修饰和唾液外切体中微小RNA的改变释放中表现出来。这种修饰可能会对不同的药物方案产生不同的反应。目前还没有其他实验研究是在多年接触抗逆转录病毒药物的背景下研究KSHV的病理生物学。这是对PA-10-290/在艾滋病毒/艾滋病背景下的恶性肿瘤研究(R01)的响应而提出的续签申请。

DESCRIPTION (provided by applicant): Today the majority of human immune deficiency virus (HIV) infected patients in the US are on long-term (10+ years) antiretroviral therapy (ART). While ART suppresses HIV replication to below 50 copies / ml, not much is known about the long-term effect of these ART drugs on Kaposi sarcoma associated herpesvirus (KSHV) transmission and disease. We hypothesize that ART drug exposure contributes directly to a restriction in KSHV gene expression. If so, the mechanism could manifest itself in epigenetic modification of the viral episome and in altered release of micro RNAs in salivary exosomes. Such modification may respond differently to different drug regimens. Currently no other experimental studies investigate KSHV pathobiology in the background of multi-year exposure to ART drugs. This is a renewal application in response to PA-10- 290/Research on Malignancies in the Context of HIV/AIDS (R01).