Role of Adenovirus Core Proteins in Innate Signaling and Viral Genome Packaging

描述(由申请人提供)：具有线性dsDNA基因组的病毒，如腺病毒(Ad)和疱疹病毒，会遇到许多宿主细胞反应，可能严重抑制病毒复制。线性病毒基因组的开放端触发了细胞DNA损伤反应(DDR)。如果不减弱，DDR会严重抑制Ad DNA复制。主要的Ad核心蛋白，蛋白VII，在感染后立即保护病毒基因组不被DDR识别。在病毒感染的早期阶段，当蛋白VII从Ad基因组中释放出来时，Ad通过替代机制抑制DDR，从而允许有效的病毒复制。核心蛋白VII与腺病毒颗粒衣壳内的病毒基因组紧密相关。目前尚不清楚在病毒组装过程中，蛋白VII是如何包装到Ad衣壳中的。一种在病毒感染期间有条件地表达Ad核心蛋白VII的方法已经被开发出来。这一方法将被用来研究Ad核心蛋白VII在病毒复制周期的各个方面的功能。这些研究不仅与Ad有关，而且与更复杂的dsDNA病毒有关，如疱疹病毒。近年来，ADS已被认为是免疫功能低下患者的重要病原体。在年轻人、老年人和军人中，AD感染也与严重的呼吸道疾病有关。目前尚无针对Ad感染的病毒特异性治疗方法。因此，为了促进抗病毒治疗的发展，充分了解Ad复制周期变得越来越重要。 公共卫生相关性：这项研究的重点是腺病毒复制过程中的早期和晚期事件。近年来，腺病毒已被认为是免疫功能低下患者的重要病原体。目前尚无针对腺病毒感染的病毒特异性治疗方法，因此，为了促进抗病毒治疗的发展，充分了解病毒的复制周期变得越来越重要。

DESCRIPTION (provided by applicant): Viruses with linear, dsDNA genomes, such as the adenoviruses (Ad) and herpesviruses, encounter a number of host cell responses that may severely inhibit virus replication. The open ends of the linear viral genomes trigger a cellular DNA damage response (DDR). A DDR severely inhibits Ad DNA replication if unabated. The major Ad core protein, protein VII, protects the viral genome from recognition by the DDR immediately after infection. As protein VII is released from the Ad genome during the early phase of viral infection, Ad inhibits a DDR by alternative mechanisms to allow efficient viral replication. Core protein VII is tightly associated with the viral genome within the Ad virus particle, the capsid. It is not clear how protein VII is packaged into the Ad capsid during virus assembly. A means to conditionally express Ad core protein VII during viral infection has been developed. This approach will be used to study the functions of Ad core protein VII during all aspects of the virus replication cycle. These studies pertain not only to Ad, but to more complex dsDNA viruses such as the herpesviruses. Ads have been recognized in recent years as significant pathogens in immunocompromised patients. Ad infection is also associated with severe respiratory disease in the young, elderly, and in military personnel. There is no virus-specific therapy for Ad infection. Thus, it has become increasingly important to fully understand the Ad replication cycle in order to foster the development of antiviral therapies. PUBLIC HEALTH RELEVANCE: This research focuses on early and late events during adenovirus replication. Adenoviruses have been recognized in recent years as significant pathogens in immunocompromised patients. There is no virus-specific therapy for adenovirus infection, thus it has become increasingly important to fully understand the virus replication cycle in order to foster the development of antiviral therapies.