MHV INDUCED APOPTOSIS AND RESISTANCE TO LETHAL HEPATITIS

MHV 诱导细胞凋亡和对致命性肝炎的抵抗

• 批准号: 6046117
• 负责人: JULIAN L LEIBOWITZ
• 金额: $ 19.21万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-15 至 2002-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6046117
• 关键词: BCL2 gene /protein; CD95 molecule; animal viral hepatitis; apoptosis; cysteine endopeptidases; disease /disorder model; double stranded RNA; genetic strain; host organism interaction; laboratory mouse; macrophage; microorganism immunology; murine hepatitis virus; p53 gene /protein; protease inhibitor; protein kinase; tissue /cell culture; tumor necrosis factor alpha; virus infection mechanism

We proposes to utilize the mouse hepatitis virus model of fulminant hepatitis In fully susceptible strains of mice, mouse hepatitis virus, strain 3(MHV-3) produces a lethal fulminant hepatitis characterized by massive hepatocellular necrosis. In contrast, resistant strains of mice survive the infection without detectable evidence of hepatic injury. We have recently observed that MHV-3 induces the rapid induction of apoptosis in infected macrophages derived from strain A/J mice, while replicating rapidly and efficiently in Balb/c derived macrophages. This rapid onset of apoptosis is correlated with inhibition of MHV induced syncytia formation and thus virus spread. We proposed to determine if the rapid induction of apoptosis by MHV-3 is confined to macrophages or also occurs in other cell types, and to delineate pathways and regulators of MHV-3 induce apoptosis using biochemical, pharmacologic, and genetic approaches. Specifically the role of caspases, bc1-2, p53, TNFa, Fas-FasL, and the dsRNA activated protein kinase PKR, in regulating MHV-3 triggered cell suicide will he studied. Furthermore it is proposed to investigate the role of the apoptotic response to resistance to lethal hepatitis by manipulating the apoptotic pathways triggered by MHV-3 we propose to investigate the role of the apoptotic response to resistance to lethal hepatitis.

我们提出利用小鼠暴发性肝炎病毒模型

项目成果

Caspase inhibitors block MHV-3 induced apoptosis and enhance viral replication and pathogenicity.

Caspase 抑制剂可阻断 MHV-3 诱导的细胞凋亡并增强病毒复制和致病性。

• DOI: 10.1007/978-1-4615-1325-4_17
• 发表时间: 2001
• 期刊: Advances in experimental medicine and biology
• 作者: Leibowitz,JL;Belyavskaya,E
• 通讯作者: Belyavskaya,E