In Vivo Analysis of Viral Cyclin

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， 清除，随后建立与宿主免疫平衡的潜伏感染 健康主机的生命周期。伽玛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、基因组结构、嗜性和相关的病理学而相关。 潜伏感染的细胞表达一组有限的病毒基因，但仍然能够重新激活裂解感染 在刺激下。潜伏期和潜伏期的再激活与慢性疾病有关， 恶性肿瘤，特别是免疫功能低下的宿主。病毒感染的调节是一个复杂的过程 宿主与病毒因子的关系。这些过程，从最初的感染到潜伏期， 重新激活，没有得到很好的理解，并受到高等教育困难的限制。 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， 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作为研究细胞的模型系统 在病毒感染中的周期调节表明，gHV 68病毒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作为癌基因发挥作用。gHV 68病毒周期蛋白 对于溶解性感染的任何方面都不是必需的，但是对于从潜伏期有效地再激活是必需的。这 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。第一，什么是 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 体内病毒细胞周期蛋白的底物？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？

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?