In Vivo Analysis of Viral Cyclin

病毒周期的体内分析

• 批准号: 6884892
• 负责人: Linda F. Van Dyk
• 金额: $ 24.71万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6884892
• 关键词: Gammaherpesvirinae; RNA interference; antiserum; artificial chromosomes; cell line; cyclins; disease /disorder model; gene expression; green fluorescent proteins; host organism interaction; laboratory mouse; latent virus infection; monoclonal antibody; protein structure function; recombinant virus; virus infection mechanism; virus protein

In Vivo Analysis of Viral Cyclin: Infection by herpesviruses causes an acute lytic infection that is rapidly cleared, and subsequent establishment of a latent infection that exists in balance with the host immune system for the lifetime of a healthy host. The gammaherpesviruses include the human pathogens, Epstein Barr virus and Kaposi's sarcoma herpesvirus, and the murine gammaherpesvirus-68 (gHV68). These viruses are related by sequence conservation, genomic organization, tropism, and associated pathologies. Latently infected cells express a limited set of viral genes, yet remain capable of reactivating lytic infection upon stimulation. Latency and reactivation from latency are associated with chronic disease and malignancies, particularly in immunocompromised hosts. Regulation of viral infection is a complex relationship between host and viral factors. These processes, from initial infection to latency and reactivation, are not well understood and have been constrained by the difficulties of studying higher mammalian host systems. The murine gHV68 model system provides a tractable small animal model in which both pathogen and host are genetically manipulable, and enables study of virus and host interactions through the entire course of viral infection. Previous utilization of gHV68 as a model system to study cell cycle regulation in viral infection demonstrated that the gHV68 viral cyclin promotes cell cycle progression and acts as an oncogene when expressed as a transgene in primary lymphocytes. The gHV68 viral cyclin is not required for any aspect of lytic infection, but is essential for efficient reactivation from latency. This proposal will address the mechanism of action of the gHV68 viral cyclin in infection. First, what is the expression pattern of the viral cyclin in infection? Second, what are the catalytic partners and the substrates of the viral cyclins in vivo? Third, are the unique features of the viral cyclins essential to their role in viral infection?

病毒细胞周期蛋白的体内分析：疱疹病毒感染会引起急性裂解感染，并迅速清除，随后建立了与宿主免疫系统保持平衡的潜在感染。伽马广播病毒包括人类病原体，爱泼斯坦Barr病毒和Kaposi的肉瘤疱疹病毒，以及鼠γγ腺病病毒-68（GHV68）。这些病毒是通过序列保守，基因组组织，端主和相关病理学的相关性。潜在感染的细胞表达有限的病毒基因，但仍能够在刺激后重新激活裂解感染。潜伏期与慢性疾病和恶性肿瘤有关，特别是在免疫功能低下的宿主中。病毒感染的调节是宿主和病毒因素之间的复杂关系。从初始感染到潜伏期和重新激活的这些过程尚未充分理解，并且受到研究较高的哺乳动物宿主系统的困难所束缚。 Murine GHV68模型系统提供了一种可拖动的小动物模型，在该模型中，病原体和宿主都是遗传操作的，并可以研究病毒和宿主相互作用 在整个病毒感染过程中。 GHV68作为模型系统的先前利用来研究病毒感染中的细胞周期调节表明，GHV68病毒细胞周期蛋白会促进细胞周期的进展，并在原发性淋巴细胞中以转基因表示为转基因。对于裂解感染的任何方面，GHV68病毒细胞周期蛋白不需要，但对于潜伏期有效重新激活至关重要。该建议将解决GHV68病毒细胞周期蛋白在感染中的作用机理。首先，感染中病毒细胞周期蛋白的表达模式是什么？第二，体内病毒细胞周期蛋白的催化伴侣和底物是什么？第三，是病毒细胞周期蛋白的独特特征 在病毒感染中？