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）：人类伽玛疱疹病毒是EB病毒（EBV）和卡波西肉瘤相关疱疹病毒（KSHV），也称为人类疱疹病毒8型（HHV-8）。每种人类伽马疱疹病毒都与多种恶性肿瘤密切相关，特别是在免疫抑制的移植受者或因同时感染人类免疫缺陷病毒而出现免疫抑制的个体中。与其他疱疹病毒一样，伽马疱疹病毒的特点是能够在宿主细胞中建立潜伏期。潜伏期的重新激活和随后的裂解性病毒复制是伽马疱疹病毒生命周期的重要组成部分，使病毒能够传播到宿主内的其他细胞或其他易感宿主。人们越来越了解伽马疱疹病毒再激活过程的分子机制，但触发这些分子事件的特定外源刺激尚未明确。临床和实验证据表明，与第二种病原体的共感染可能会刺激潜伏感染伽马疱疹病毒的宿主重新激活。该应用程序将使用小鼠双重感染模型来测试以下假设：第二种病原体的急性感染能够诱导潜伏的鼠伽马疱疹病毒 68 (MHV-68) 重新激活。具体目标是 1) 确定共感染是否会诱导潜伏 MHV-68 重新激活，2) 确定选定的趋化因子和细胞因子在潜伏 MHV-68 重新激活中的作用。与公共卫生的相关性：本申请中概述的实验将扩大我们对伽马疱疹病毒如何重新激活的理解，即从持续感染者的非活动状态中唤醒，以创建能够感染同一人体内其他细胞或感染其他细胞的新病毒副本。个人。从这些实验中获得的信息将极大地促进我们对伽马疱疹病毒生物学和发病机制的理解，并可能对旨在治疗伽马疱疹病毒相关疾病的策略产生影响。