In Vivo Analysis of Viral Cyclin

在病毒周期蛋白的活体分析中：疱疹病毒感染会引起急性裂解性感染，这种感染会迅速清除，随后会建立一种潜伏感染，在健康宿主的一生中与宿主免疫系统保持平衡。伽马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，以及小鼠伽马疱疹病毒-68(GHV68)。这些病毒与序列保守性、基因组组织、嗜性和相关的病理学有关。潜伏感染的细胞表达一组有限的病毒基因，但仍能在刺激下重新激活裂解感染。潜伏期和潜伏期的重新激活与慢性病和恶性肿瘤有关，特别是在免疫受损的宿主中。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，从最初的感染到潜伏和重新激活，还没有被很好地理解，并且受到研究高等哺乳动物寄主系统的困难的限制。小鼠ghv68模型系统提供了一个易于处理的小动物模型，在该模型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之间的相互作用。 在病毒感染的整个过程中。以前利用gHV68作为研究病毒感染中细胞周期调控的模型系统表明，gHV68病毒周期蛋白在原代淋巴细胞中以转基因的形式表达时，促进了细胞周期的进展，并发挥了癌基因的作用。GHV68病毒周期蛋白对溶血性感染的任何方面都不是必需的，但对于从潜伏期有效地重新激活是必不可少的。这项提案将解决gHV68病毒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，病毒周期蛋白在体内的催化伙伴和底物是什么？第三，病毒周期蛋白的独特特性是否对它们的作用至关重要？ 在病毒感染中？

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?