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(申请人提供)：卡波西肉瘤是一种 与KS相关感染密切相关的内皮肿瘤 疱疹病毒，KSHV。KSHV是一种嗜淋巴病毒，其主要宿主是 B细胞。因此在KS发病机制中需要向其内皮靶点扩散 潜伏感染的B细胞的重新激活和裂解复制。此外, 越来越多的证据表明，KSHV裂解循环可能是 影响KS血管生成和炎症的旁分泌因素， KS的组织学特征。在此应用程序中，建议进行以下实验 检查裂解KSHV重新激活和传播的分子基础 (I)关键调节因子病毒RTA蛋白的生化机制 潜伏-裂解开关，调节病毒基因表达，本身就是 (2)裂解病毒重新激活对宿主细胞的影响 存活和基因表达；以及(Iii)识别宿主细胞表面分子 参与了KSHV的进入和传播。