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，迅速清除，随后建立潜伏感染，与宿主免疫系统在健康宿主的一生中保持平衡。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，以及小鼠伽玛疱疹病毒-68 （gHV68）。这些病毒在序列保守性、基因组组织、趋向性和相关病理方面具有相关性。潜伏感染的细胞表达一组有限的病毒基因，但仍然能够在刺激下重新激活裂解性感染。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与病毒因子之间复杂的关系。这些过程，从最初的感染到潜伏和再激活，尚未得到很好的理解，并受到研究高等哺乳动物宿主系统的困难的限制。小鼠gHV68模型系统提供了一种易于处理的小动物模型，其中病原体和宿主在遗传上都是可操纵的，并且可以研究病毒和宿主的相互作用

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?