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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景：卡波西肉瘤（KS）是一种与HIV感染相关的血管性肿瘤，常发生于口腔。 卡波西肉瘤相关疱疹病毒（KSHV），也称为人类疱疹病毒8（HHV 8）的感染，在过去十年中已被确定为KS的病因。 已经表明，HIV感染通过直接的HIV-病毒相互作用或宿主因子（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感染和脱落在口腔中的艾滋病毒感染的受试者。 目的：本研究计划的长期目标是了解KSHV诱导发病的分子机制，为预防和治疗目的提供科学依据。 本申请的目的是研究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，并因此调节口腔中的KSHV感染、潜伏期和再激活。 将追求两个具体目标：1）检查口腔中HIV感染对KSHV病毒载量和基因型的调节;和2）检查口腔中HIV感染对KSHV潜伏期和再激活的调节。 临床相关性：我们在KSHV研究方面已经建立了广泛的跟踪记录，并且已经开发了该项目所需的各种技术和相关试剂。 这项拟议的研究意义重大，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.