Mechanisms of KSHV Transmission

项目摘要 Kaposi肉瘤相关疱疹病毒主要通过唾液传播， 包括精液和母乳。KSHV存在较大差异 不同人群的血清阳性率。在美国小于10%，但在KSHV地方病中大于50 撒哈拉以南非洲地区。而美国的艾滋病-KS流行是由反复接触驱动的 在流行地区，KSHV在男男性行为者中是在儿童时期获得的。我们正在回应RFA-CA-18- 013破译KSHV是如何传输的。本应用程序的总体目标是了解 KSHV的分子传播，最终目标是为疫苗设计提供信息， 找出其他阻断传播的方法。为了实现这一目标，我们将研究三大支柱 传染性病原体的传播性：（i）KSHV菌株之间的差异，使用现有的标本， 大型临床队列，（ii）对KSHV感染的先天免疫应答之间的差异，以及（iii） 微生物组的变化可能影响KSHV本身（通过局部病毒载量测量）和 对感染的先天免疫反应在每一种情况下，我们都将从描绘自然的人类变异开始， 然后探索重要病毒和宿主变异体在进入功能测定中的功能， 复制和传播。

Project Summary Abstract Kaposi's Sarcoma-associated herpesvirus is transmitted primarily by saliva, though other routes including semen and breastmilk have also been described. There exists a big discrepancy in KSHV seroprevalence across different populations. It is less than 10% in the US, but > 50% in KSHV endemic regions in Sub-Saharan Africa. Whereas the US AIDS-KS epidemic was driven by repeated contact among MSM, in endemic regions KSHV is acquired in childhood. We are responding to RFA-CA-18- 013 to decipher how KSHV is transmitted. The overall goal of this application is to understand the transmission of KSHV in molecular terms, with the ultimate goal being to inform vaccine design and identify other means of disrupting transmission. To achieve this goal, we will investigate the three pillars of transmissibility of infectious agents: (i) variance among KSHV strains using existing specimens from large clinical cohorts, (ii) variance among the innate immune responses to KSHV infection, and (iii) variance in the microbiome which may affect both KSHV itself (as measured by local viral load) and the innate immune response to infection. In each case, we will start by profiling natural human variation and then explore the function of significant viral and host variants in functional assays for entry, replication and transmission.