KSHV Modulation of Type I Interferon

描述(申请人提供)：疱疹感染是世界上存在的最常见的病毒感染之一。这些病毒可能是亚临床的，或者就卡波西肉瘤相关疱疹病毒(KSHV)而言，它们可能导致癌症等危险疾病。众所周知，KSHV在艾滋病患者中会导致卡波西氏肉瘤(KS)和其他几种淋巴增生性疾病。这些病毒在口腔内引起感染，并可经口腔传播。这个应用程序的总体目标是定义KSHV之间的交互 以及病毒在口腔中感染细胞中引发的先天免疫反应。我们将重点介绍KSHV感染的先天免疫反应，特别是I型干扰素反应。众所周知，I型干扰素是人体的天然抗病毒系统，几乎所有导致人类感染的病毒都有阻止或利用这一系统增强其在宿主中复制的方法。该项目的目标是开发基于先天免疫的新型疗法，利用先天免疫系统的力量直接阻止KSHV复制。我们是第一个确定先天性免疫系统如何识别疱疹病毒(包括KSHV)的小组，并定义了诱导(来自宿主端)和阻止(来自病毒端)干扰素的信号机制。此应用程序 是为了确定这些系统如何相互作用而导致感染和疾病。这笔R03拨款的长期工作将建立初步数据，以申请更大的R01拨款，这将 探索如何调节这些机制来对抗KSHV感染和相关疾病。

DESCRIPTION (provided by applicant): Herpes infections represent one of the most common viral infections that exist in the world. These viruses can be subclinical or as in the case of Kaposi's Sarcoma Associated Herpesvirus (KSHV) they can lead to dangerous diseases such as cancer. KSHV is well known in AIDS patients to cause Kaposi's Sarcoma (KS) and several other lymphoproliferative diseases. These viruses setup infection in oral cavities and can be transmitted orally. The overall goal of this application is to define the interactions between KSHV and the innate immune response the virus elicits in infected cells in the oral cavity. We will focu on the innate immune response to KSHV infection, especially the Type I Interferon response. Type I Interferon is well known to be the body's natural anti-viral system and almost all viruses that cause infection in humans have devolved ways to block or use this system to enhance their replication in the host. The goal of this project is to lead to the development of novel, innate immune based therapeutics harnessing the power of the innate immune system to directly stop KSHV replication. We were the first group to determine how the innate immune system can recognize herpesviruses (including KSHV) and have also defined the signaling mechanisms that induce interferon (from the host side) and block interferon (from the virus side). This application is setup to determine how these systems interact together to lead to infection and disease. Long term work from this R03 grant will setup preliminary data to apply for a larger R01 grant that will explore how these mechanisms can be modulated to fight KSHV infection and associated diseases.