APOPTOSIS DURING HSV INFECTION

HSV 感染期间的细胞凋亡

• 批准号: 6471140
• 负责人: John A. Blaho
• 金额: $ 29.66万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6471140
• 关键词: apoptosis; clinical research; gene expression; herpes simplex virus 1; host organism interaction; human fetus tissue; human tissue; protein biosynthesis; regulatory gene; temperature sensitive mutant; tissue /cell culture; transfection; virus infection mechanism

DESCRIPTION (provided by applicant): Human herpes simplex viruses (HSV-1 and HSV-2) cause significant morbidity and mortality in neonatal and immunocompromised populations. HSVs are cytolytic viruses which have profound impacts on their host cells. Consequences of HSV-1 infection of cultured cells include the induction of apoptosis and the concomitant synthesis of protein(s) which act to block this process. The broad, long-term objective of our research program is to determine the function of viral and cellular factors involved in apoptosis during HSV-1 infection of human cells. In this project, we are identifying the factors/events that trigger apoptosis during infection and the genes encoding the proteins responsible for its prevention. We showed that HSV-1 induction of apoptosis in human cells occurs in the absence of de novo viral protein synthesis. Our preliminary data indicates that viral entry is not sufficient to induce the process. In our first aim, the hypothesis which we are testing is that the initiation of viral gene expression is the trigger of apoptosis in infected human cells. We also showed that an anti-apoptotic activity is synthesized between 3 and 6 hours after HSV-1 infection of human cells. In our second aim, the hypothesis we are testing is that virally-induced factor(s) are responsible for the anti-apoptotic function. The goal of these studies is to isolate genes involved in blocking of apoptosis during infection using a combination of biochemical and molecular genetic techniques. These studies are designed to help elucidate the complexities of apoptotic programmed cell death during the replication of this important human pathogen.

描述（由申请人提供）：人类单纯疱疹病毒（HSV-1和 HSV-2）在新生儿和 免疫功能低下的人群。 HSV是具有深刻的胞溶病毒 影响其宿主细胞。 HSV-1感染培养细胞的后果 包括诱导凋亡和蛋白质的伴随合成 哪个行动可以阻止此过程。我们研究的广泛，长期目标 程序是确定涉及的病毒和细胞因素的功能 人类细胞HSV-1感染期间的凋亡。在这个项目中，我们是 确定在感染期间触发凋亡的因素/事件和事件 编码负责预防的蛋白质的基因。我们表明了这一点 HSV-1诱导人类细胞中凋亡的诱导发生在没有从头的情况下发生 病毒蛋白质合成。我们的初步数据表明病毒输入不是 足以诱导该过程。在我们的第一个目标中，我们是的假设 测试是病毒基因表达的启动是 感染人类细胞的凋亡。我们还表明了抗凋亡 HSV-1感染后3至6小时合成活性 细胞。在我们的第二个目标中，我们正在检验的假设是病毒诱导的 因子负责抗凋亡功能。这些目标 研究是为了隔离参与感染过程中凋亡的基因 结合生化和分子遗传技术。这些 研究旨在帮助阐明凋亡编程的复杂性 在这种重要人类病原体复制过程中的细胞死亡。