CHARACTERIZATION OF THE GAMMA HV68 V CYCLIN

GAMMA HV68 V CYCLIN 的特性

• 批准号: 6514680
• 负责人: SAMUEL H SPECK
• 金额: $ 32.4万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6514680
• 关键词: Gammaherpesvirinae; Herpesviridae disease; cyclins; laboratory mouse; latent virus infection; pathologic process; protein structure function; viral carcinogenesis; virulence; virus genetics; virus protein

This is a new RO1 grant proposal to investigate the mechanisms by which cyclin homologs encoded by gamma-Herpesviruses (v-cyclin) contribute to gamma-herpesvirus pathogenesis and latency. The human gamma-herpesviruses, KSHV and EBV, are important causes of cancer especially in immunocompromised individuals. Because of the species specificity of these viruses, in vivo studies of their pathogenesis have been limited. This proposal makes use of a small animal model system, infection of inbred mice with gammaHV68, for analysis of the pathogenesis of gamma-herpesvirus infection and the role of individual gamma-herpesvirus genes in latency and tumor induction. GammaHV68 infection is associated with the development of lymphoma and lymphoproliferative disease, severe vasculitis of the great elastic vessels and splenic fibrosis. Studies to date indicate the gammaHV68 shares pathogenetic mechanisms with EBV, KSHV, and HVS, validating it as a model for analysis of important questions in gammaherpesvirus pathogenesis. This grant is focused on the role of the gammaHV68 v-cyclin in disease pathogenesis. Notably, the gamma2- herpesviruses (HVS, KSHV and gammaHV68) all encode homologs of D-type cyclins, while EBV infection upregulates expression of host D-type cyclins. The investigators have shown that the gammaHV68 v-cyclin is an oncogene that promotes cell cycle progression in primary lymphocytes and that a gammaHV68 v-cyclin mutant reactivates inefficiently from latently infected Msigma and/or B cells. These observations lead to the following 3 specific aims of this proposal: 1) Determine the role(s) of the gammaHV68 v-cyclin in latency and reactivation. 2) Characterize regulation of gammaHV68 v-cyclin expression. 3) Determine the structural and biochemical basis of differences in the functions of the gammaHV68 v-cyclin and host D and E type cyclins.

这是一项新的RO1拨款提案，旨在通过