HOST/VIRUS INTERACTION AND GENE EXPRESSION

宿主/病毒相互作用和基因表达

• 批准号: 6124257
• 负责人: Amiya K. Banerjee
• 金额: $ 29.72万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6124257
• 关键词: DNA directed RNA polymerase; Paramyxovirus; actin binding protein; actins; autoradiography; chemical association; confocal scanning microscopy; cytoskeletal proteins; enzyme activity; enzyme inhibitors; gene expression; genetic regulatory element; genetic transcription; glyceraldehyde 3 phosphate dehydrogenase; isozymes; nucleocapsid; phosphorylation; protein kinase C; protein structure function; ribonucleoproteins; tissue /cell culture; virus genetics; virus infection mechanism; virus protein; virus replication

DESCRIPTION (Adapted from Applicant's Abstract): The long term goal of this renewal application is to study in detail the involvement of host proteins in the gene expression of the respiratory pathogen human parainfluenza virus type 3 (hPIV3). HPIV3 is a common causative agent for acute respiratory tract disease of infants and children. Effective vaccines to combat hPIV3 infection are not currently available. During the continuing studies of this group in the important area of host-virus interaction, they have discovered a number of cellular proteins that interact either with virus-encoded proteins or cis-regulatory RNA elements. These include cytoskeletal protein actin, involved in transcription of virus genome RNA; cellular protein kinase C, isoform z, which specifically phosphorylated hPIV3 phosphoprotein P to activate it for eventual replication of the virus; cellular La protein and ubiquitous cellular enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which specifically interact with cis-regulatory viral RNAs. Additionally they have demonstrated that the cellular MxA protein, an interferon-inducible protein, inhibits hPIV3 replication, setting the stage to study the role of host proteins in cell defense mechanisms. They propose to study in detail the role of these cellular proteins in the hPIV3 life cycle, focussing on their actions on the virus's transcriptive and replicative pathways. They will study the molecular basis underlying such specific interactions between these host proteins and viral components. They also propose experiments to counteract some of these host-virus interactive steps that would help create an opportunity to develop antiviral agents. Understanding in detail the molecular basis of the interplay of viruses and cellular proteins would further our knowledge to understand the role of the host in promoting or abrogating virus replication and develop agents that specifically target certain host-virus interactions.

描述（改编自申请人的摘要）：本发明的长期目标是： 更新应用是详细研究宿主蛋白质的参与 呼吸道病原体人类副流感病毒的基因表达 3型（hPIV 3）。 HPIV 3是急性呼吸道感染的常见病原体， 婴儿和儿童的肠道疾病。 对抗hPIV 3的有效疫苗 感染目前不可用。 在继续研究期间， 在宿主-病毒相互作用的重要领域， 发现了一些细胞蛋白质， 病毒编码的蛋白质或顺式调节RNA元件。 这些包括 细胞骨架蛋白肌动蛋白，参与病毒基因组RNA的转录; 细胞蛋白激酶C，亚型z，特异性磷酸化 hPIV 3磷蛋白P，以激活其用于病毒的最终复制; 细胞La蛋白和普遍存在的细胞酶， 甘油醛-3-磷酸脱氢酶（GAPDH），其特异性相互作用 顺式调节病毒RNA。 此外，他们还证明， 细胞MxA蛋白是一种干扰素诱导蛋白， 复制，为研究宿主蛋白在细胞中的作用奠定了基础。 防御机制 他们建议详细研究这些机构的作用， hPIV 3生命周期中的细胞蛋白，重点关注它们对 病毒的转录和复制途径。 他们将研究 这些宿主之间这种特异性相互作用的分子基础 蛋白质和病毒成分。 他们还提出了一些实验来抵消 其中一些主机-病毒交互步骤有助于创建一个 开发抗病毒药物的机会。 详细了解 病毒和细胞蛋白相互作用的分子基础将 进一步了解我们的知识，以了解主机在促进或 消除病毒复制并开发特异性靶向 某些宿主与病毒的相互作用