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

描述（由申请人提供）：具有线性双链DNA基因组的病毒，例如腺病毒（Ad）和疱疹病毒，会遇到许多可能严重抑制病毒复制的宿主细胞反应。线性病毒基因组的开放端会触发细胞 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。由于蛋白质 VII 在病毒感染的早期阶段从 Ad 基因组中释放，Ad 通过替代机制抑制 DDR，以实现病毒的有效复制。核心蛋白 VII 与 Ad 病毒颗粒衣壳内的病毒基因组紧密相关。目前尚不清楚蛋白质 VII 在病毒组装过程中如何包装到 Ad 衣壳中。已经开发出一种在病毒感染期间条件性表达 Ad 核心蛋白 VII 的方法。该方法将用于研究 Ad 核心蛋白 VII 在病毒复制周期各个方面的功能。这些研究不仅涉及 Ad，还涉及更复杂的 dsDNA 病毒，例如疱疹病毒。近年来，广告已被认为是免疫功能低下患者的重要病原体。 Ad 感染还与年轻人、老年人和军事人员的严重呼吸道疾病有关。目前尚无针对 Ad 感染的病毒特异性疗法。因此，充分了解 Ad 复制周期以促进抗病毒疗法的发展变得越来越重要。 公共卫生相关性：本研究重点关注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。目前还没有针对腺病毒感染的病毒特异性疗法，因此充分了解病毒复制周期以促进抗病毒疗法的发展变得越来越重要。

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.