ORAL KSHV (KAPOSI'S SARCOMA HERPES VIRUS) COMPLICATIONS IN HIV INFECTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景：卡波西肉瘤(Kaposi‘s Saroma，KS)是一种与HIV感染相关的血管肿瘤，多见于口腔。在过去的十年里，Kaposi肉瘤相关疱疹病毒(KSHV)的感染，也被称为人类疱疹病毒8型(HHV8)，已经被证实是KS的病因。已有研究表明，HIV感染通过HIV与病毒的直接相互作用或宿主因素(包括免疫系统细胞因子)的改变来调节其他病毒感染。几项研究也证明了KSHV在HIV感染者的口腔中感染和脱落。 目的：本研究的长期目标是了解KSHV致病的分子机制，为预防和治疗提供科学依据。这项应用的目的是检查HIV和KSHV在口咽环境中相互作用的分子基础，以检验HIV感染改变口腔环境的中心假设，从而调节KSHV在口腔中的感染、潜伏和重新激活。有两个特定的目标：1)研究口腔内HIV感染对KSHV病毒载量和基因类型的调节；2)研究口腔内HIV感染对KSHV潜伏期和再激活的调节。 临床意义：我们在KSHV研究方面建立了广泛的跟踪记录，并已经开发了该项目所需的各种技术和相关试剂。这项拟议的研究具有重要意义，因为它将定义口腔中HIV-KSHV相互作用的生物学和病毒学，并可能确定新的治疗靶点。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. BACKGROUND: Kaposi's sarcoma (KS) is a vascular neoplasm associated with HIV infection and often manifests in the oral cavity. Infection of Kaposi's sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV8), has been well established as the etiology of KS in the past decade. It has been shown that HIV infection modulates other viral infections via either direct HIV-virus interactions or alterations of host factors, including the immune system cytokines. Several studies have also demonstrated KSHV infection and shedding in the oral cavity of HIV-infected subjects. OBJECTIVE: The long-term goal of our research program is to understand the molecular mechanism of KSHV-induced pathogenesis, providing a scientific basis for preventive and therapeutic purposes. The objective of this application is to examine the molecular basis of interactions between HIV and KSHV in the oropharyngeal environments in order to test the central hypothesis that HIV infection alters oral environments, and as a result, modulates KSHV infection, latency and reactivation in the oral cavity. Two specific aims will be pursued: 1) To examine the modulation of KSHV viral loads and genotypes by HIV infection in the oral cavity; and 2) To examine the modulation of KSHV latency and reactivation by HIV infection in the oral cavity. CLINICAL RELEVANCE: We have established an extensive track record in KSHV research, and have already developed various technologies and related reagents that are needed for this project. The proposed study is significant because it will define the biology and virology of HIV-KSHV interactions in the oral cavity, and potentially identify novel therapeutic targets.