In Vivo Analysis of Viral Cyclin

病毒周期的体内分析

• 批准号: 7119331
• 负责人: Linda F. Van Dyk
• 金额: $ 3.38万
• 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/7119331
• 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?

病毒周期蛋白的体内分析：疱疹病毒感染引起急性溶解性感染，该感染被迅速清除，随后建立潜伏性感染，该感染在健康宿主的一生中与宿主免疫系统平衡存在。γ疱疹病毒包括人类病原体，爱泼斯坦巴尔病毒和卡波西肉瘤疱疹病毒，以及鼠γ疱疹病毒-68（gHV 68）。这些病毒通过序列保守性、基因组组织、嗜性和相关病理学而相关。潜伏感染的细胞表达一组有限的病毒基因，但仍然能够在刺激后重新激活裂解感染。潜伏期和潜伏期的再激活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。病毒感染的调控是宿主和病毒因子之间的复杂关系。这些过程，从最初的感染，潜伏期和重新激活，没有得到很好的理解，并已受到限制的困难，研究高等哺乳动物宿主系统。鼠gHV 68模型系统提供了一种易于处理的小动物模型，其中病原体和宿主都是可遗传操纵的，并且能够研究病毒和宿主的相互作用 在病毒感染的整个过程中。先前利用gHV 68作为模型系统来研究病毒感染中的细胞周期调控，证明了gHV 68病毒细胞周期蛋白促进细胞周期进展，并且当在原代淋巴细胞中作为转基因表达时充当癌基因。gHV 68病毒细胞周期蛋白对于裂解性感染的任何方面都不是必需的，但对于从潜伏期有效再激活是必需的。该提案将阐述gHV 68病毒细胞周期蛋白在感染中的作用机制。首先，病毒周期蛋白在感染中的表达模式是什么？第二，病毒细胞周期蛋白在体内的催化伴侣和底物是什么？第三，病毒细胞周期蛋白的独特特征是否对其作用至关重要 在病毒感染？