Inflammatory Mediators of Gammaherpesvirus Reactivation

伽玛疱疹病毒再激活的炎症介质

• 批准号: 7037760
• 负责人: Jason Brice Weinberg
• 金额: $ 19.13万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-02 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7037760
• 关键词: 3T3 cells; Betaherpesvirinae; Epstein Barr virus; Gammaherpesvirinae; Klebsiella pneumoniae; RNase protection assay; biological models; chemokine; comorbidity; cytokine; gene expression; human herpesvirus 8; laboratory mouse; latent virus infection; microorganism culture; microorganism interaction; model design /development; nucleic acid purification; polymerase chain reaction; virus cytopathogenic effect; virus genetics; virus infection mechanism; virus load; virus protein; virus replication

DESCRIPTION (provided by applicant): The human gammaherpesviruses are Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). Each human gammaherpesvirus is closely associated with a number of malignancies, particularly in immunosuppressed transplant recipients or individuals with immunosuppression due to concurrent infection with human immunodeficiency virus. Like other herpesviruses, the gammaherpesviruses are characterized by their ability to establish latency in host cells. Reactivation from latency and subsequent lytic viral replication is an essential component of the gammaherpesvirus life cycle, allowing the virus to spread to other cells within the host or to other susceptible hosts. Molecular mechanisms underlying the process of gammaherpesvirus reactivation are increasingly understood, but specific exogenous stimuli that trigger these molecular events are not yet well defined. Clinical and experimental evidence suggests that coinfection with a second pathogen may serve as a stimulus for reactivation in a host latently infected with a gammaherpesvirus. Using a mouse model of coinfection, this application will test the hypothesis that acute infection with a second pathogen is capable of inducing reactivation of latent murine gammaherpesvirus 68 (MHV-68). The specific aims are to 1) determine whether coinfection induces reactivation of latent MHV-68, and 2) define the roles of select chemokines and cytokines in reactivation of latent MHV-68. Relevance to Public Health: The experiments outlined in this application will expand our understanding of how gammaherpesviruses reactivate, awakening from an inactive state in a persistently infected person in order to create new copies of virus capable of infecting other cells within the same person or infecting other individuals. Information gained from these experiments will contribute significantly to our understanding of gammaherpesvirus biology and pathogenesis and potentially will impact on strategies designed to treat gammaherpesvirus-related disease.

描述（由申请人提供）：人γ瘤病毒是爱泼斯坦 - 巴尔病毒（EBV）和卡波西肉瘤相关的疱疹病毒（KSHV），也称为人类疱疹病毒8（HHV-8）。每个人类伽马病毒病毒都与许多恶性肿瘤密切相关，尤其是在免疫抑制的移植受者或因与人类免疫缺陷病毒同时感染而引起的免疫抑制的个体。与其他疱疹病毒一样，γ掌病毒的特征是它们在宿主细胞中建立潜伏期的能力。潜伏期和随后的裂解病毒复制的重新激活是伽马犬生命周期的重要组成部分，使病毒可以扩散到宿主或其他易感宿主内的其他细胞。越来越多地了解γ掌病毒重新激活过程的分子机制，但是触发这些分子事件的特定外源刺激尚未得到很好的定义。临床和实验证据表明，与第二个病原体的共同感染可能是刺激刺激在被γ掌病毒的宿主中重新激活的刺激。使用共同感染的小鼠模型，该应用将检验以下假设：第二种病原体的急性感染能够诱导潜在的鼠γγ病毒68（MHV-68）重新激活。具体目的是1）确定共感染是否诱导潜在MHV-68的重新激活，以及2）定义精选趋化因子和细胞因子在潜在MHV-68重新激活中的作用。与公共卫生的相关性：本应用程序中概述的实验将扩大我们对γ鞘病毒如何重新激活的理解，从一个持续感染的人中的不活动状态唤醒，以创建能够感染同一患者中其他细胞或感染其他人的病毒的新副本。从这些实验中获得的信息将对我们对伽马病毒生物学和发病机理的理解产生重大贡献，并有可能影响旨在治疗与伽马梅病毒相关疾病的策略。