Pathophysiology of lytic reactivation and spread of KSHV

描述（由申请人提供）：卡波西肉瘤（KS）是一种 与KS相关感染密切相关的内皮肿瘤 疱疹病毒KSHV KSHV是一种嗜淋巴细胞病毒，其主要宿主是 B细胞。因此，在KS发病机制中向其内皮靶点的扩散需要 从潜伏感染的B细胞的再活化和裂解性复制。此外，本发明还提供了一种方法， 越来越多的证据表明，KSHV裂解周期可能是 影响KS血管生成和炎症的旁分泌因子， KS的组织学特征。在本申请中，提出了实验以 通过检查，研究裂解性KSHV再活化和传播的分子基础， (i)病毒RTA蛋白的生化机制， 潜伏裂解开关，调节病毒基因表达， 调节;（ii）裂解性病毒再活化对宿主细胞的影响 存活和基因表达;和（iii）鉴定宿主细胞表面分子 参与了KSHV的进入和传播

DESCRIPTION (Provided by the applicant): Kaposi's sarcoma (KS) is an endothelial neoplasm that is tightly linked to infection by KS-associated herpesvirus, KSHV. KSHV is a lymphotropic virus whose primary reservoir is the B cell. Spread to its endothelial targets in KS pathogenesis therefore requires reactivation from latently infected B cells and lytic replication. In addition, growing evidence suggests that the KSHV lytic cycle may be the source of paracrine factors that influence KS angiogenesis and inflammation, two of the histologic signatures of KS. In this application, experiments are proposed to examine the molecular basis of lytic KSHV reactivation and spread, by examining (i) the biochemical mechanisms by which the viral RTA protein, a key regulator of the latent-lytic switch, regulates viral gene expression and is itself regulated; (ii) the consequences of lytic viral reactivation on host cell survival and gene expression; and(iii) identifying host cell surface molecules involved in KSHV entry and spread.