HOST/VIRUS INTERACTION AND GENE EXPRESSION

描述(改编自申请者摘要)：该项目的长期目标 更新的应用是详细研究宿主蛋白的参与 呼吸道病原体人类副流感病毒基因表达的研究 类型3(HPIV3)。HPIV3是引起急性呼吸道疾病的常见病原体。 婴幼儿的肠道疾病。对抗hPIV3的有效疫苗 目前无法获得感染情况。在继续研究的过程中 这一群体在宿主与病毒交互的重要领域，他们有 发现了许多细胞蛋白，它们要么与 病毒编码的蛋白质或顺式调节的RNA元件。这些措施包括 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 HPIV3磷酸化蛋白P激活它以最终复制病毒； 细胞La蛋白和无处不在的细胞酶， 特异性相互作用的甘油醛-3-磷酸脱氢酶 通过顺式调控的病毒RNA。此外，他们还证明了 细胞MxA蛋白是一种干扰素诱导蛋白，可抑制hPIV3 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因素的作用 HPIV3生命周期中的细胞蛋白，重点研究它们在 病毒的转录和复制途径。他们将研究 这些宿主之间这种特定相互作用的分子基础 蛋白质和病毒成分。他们还提出了实验，以抵消 其中一些主机-病毒交互步骤将有助于创建 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是 进一步加深我们的知识，了解主持人在促进或 消除病毒复制并开发专门针对 某些主机和病毒之间的相互作用。

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.