Pathophysiology of lytic reactivation and spread of KSHV

KSHV 裂解再激活和传播的病理生理学

• 批准号: 6627764
• 负责人: DON GANEM
• 金额: $ 33.67万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627764
• 关键词: B lymphocyte; Kaposi's sarcoma; apoptosis; binding sites; cell line; cytolysis; gene expression; gene induction /repression; genetic regulation; host organism interaction; human herpesvirus 8; laboratory rabbit; latent virus infection; molecular cloning; paracrine; plasmids; posttranslational modifications; protein protein interaction; protein structure function; transfection /expression vector; virus cytopathogenic effect; virus infection mechanism; virus protein; virus receptors; virus related neoplasm /cancer

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.

描述（由申请人提供）：Kaposi的肉瘤（KS）是 内皮肿瘤与KS相关的感染紧密相关 疱疹病毒，KSHV。 KSHV是一种淋巴病毒，其主要储层是 B单元。因此，在KS发病机理中扩展到其内皮靶标需要 由潜在感染的B细胞和裂解复制重新激活。此外， 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，其中两个 KS的组织学特征。在此应用中，提出了实验 检查裂解KSHV重新激活的分子基础，并通过检查 （i）病毒RTA蛋白（关键调节剂）的生化机制 在潜在的开关中，调节病毒基因表达，自身 受监管； （ii）裂解病毒重新激活对宿主细胞的后果 生存和基因表达； （iii）识别宿主细胞表面分子 参与KSHV进入和传播。