In Vivo Analysis of Viral Cyclin

在对病毒周期蛋白的活体分析中：疱疹病毒感染会引起一种迅速的急性溶血性感染 清除，随后建立与宿主免疫平衡的潜伏感染 系统在健康的主机的生命周期内。伽马疱疹病毒包括人类病原体爱泼斯坦 Barr病毒和卡波西氏肉瘤疱疹病毒，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、嗜性和相关的病理有关。 潜伏感染的细胞表达一组有限的病毒基因，但仍有能力重新激活裂解感染 在刺激下。潜伏期和潜伏期的重新激活与慢性病和 恶性肿瘤，尤其是免疫功能受损的宿主。对病毒感染的调控是一项复杂的工作 宿主与病毒因子的关系。这些过程，从最初的感染到潜伏和 重新激活，没有被很好地理解，并且受到了学习更高的困难的限制 哺乳动物的宿主系统。小鼠ghv68模型系统提供了一个易于处理的小动物模型。 哪些病原体和宿主都是基因可操纵的，并使研究病毒和宿主的相互作用成为可能 在病毒感染的整个过程中。以前利用gHV68作为研究细胞的模型系统 病毒感染中的周期调控研究表明gHV68病毒周期蛋白促进细胞周期进程 并在原代淋巴细胞中以转基因的形式表达时，起到癌基因的作用。GHV68病毒周期蛋白 对于裂解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 该提案将解决gHV68病毒周期蛋白在感染中的作用机制。首先，什么是 病毒周期蛋白在感染中的表达模式？第二，什么是催化伙伴和 病毒周期蛋白在体内的底物？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?