Host Virus Interaction and Gene Expression

宿主病毒相互作用和基因表达

• 批准号: 6640196
• 负责人: Amiya K. Banerjee
• 金额: $ 37万
• 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 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6640196
• 关键词: DNA directed RNA polymerase; MHC class I antigen; MHC class II antigen; Paramyxovirus; RNA biosynthesis; RNA virus; actin binding protein; cell line; cytoskeletal proteins; gene expression; genetic transcription; nucleoproteins; phosphorylation; protein structure function; receptor expression; tissue /cell culture; virus genetics; virus infection mechanism; virus protein; virus replication

DESCRIPTION (provided by applicant): The long term goal of this renewal grant application is to understand the molecular mechanism of host-virus interactions and gene expression of human parainfluenza virus, type 3 (HPIV3), an important human pathogen which targets lung epithelial cells of the respiratory tract of infants and children leading to acute bronchiolitis, pneumonia and croup. Effective vaccines or antivirals to combat HPIV3 infection are currently unavailable. Our primary goal is to gain insight into some specific host-virus interactive processes which include, (b) identification and characterization of the cell surface receptors of epithelial cells (a) the role of actin binding protein, beta catenin in the transcription ability of HPIV3 ribonucleoprotein (RNP) complex and (c) regulation of expression of major histocompatibility complex II induced by HPIV3 which may play an important role in cellular immunity leading to infection-related damage to lung epithelium. We also propose to continue our studies in understanding the structure and function of the RNA polymerase, L and P proteins, of HPIV3, especially with regard to the role of phosphorylation of P protein and identification and characterization of the functional domains of L and P proteins. Finally, we wish to exploit reverse genetics using the infectious cDNA of HPIV3 constructed in our laboratory to study phenotypic characteristics of some distinctive cis-regulatory mutants. The studies proposed in this application have the potential to gain deeper insight to various host-virus interactive pathways, which may eventually lead to rational designing of antivirals, vaccines, and expression vectors.

描述（由申请人提供）：本次更新拨款申请的长期目标是了解宿主与病毒相互作用的分子机制以及人副流感病毒 3 型 (HPIV3) 的基因表达，这是一种针对肺上皮细胞的重要人类病原体婴儿和儿童呼吸道疾病，导致急性细支气管炎、肺炎和哮吼。目前尚无有效的疫苗或抗病毒药物来对抗 HPIV3 感染。我们的主要目标是深入了解一些特定的宿主-病毒相互作用过程，其中包括：（b）上皮细胞的细胞表面受体的鉴定和表征（a）肌动蛋白结合蛋白、β连环蛋白在 HPIV3 转录能力中的作用核糖核蛋白 (RNP) 复合物和 (c) HPIV3 诱导的主要组织相容性复合物 II 表达的调节，这可能在导致肺上皮感染相关损伤的细胞免疫中发挥重要作用。 我们还建议继续研究了解 HPIV3 的 RNA 聚合酶、L 和 P 蛋白的结构和功能，特别是 P 蛋白磷酸化的作用以及 L 和 P 蛋白功能域的鉴定和表征。最后，我们希望利用我们实验室构建的 HPIV3 感染性 cDNA 进行反向遗传学来研究一些独特的顺式调控突变体的表型特征。 本申请中提出的研究有可能更深入地了解各种宿主-病毒相互作用途径，这可能最终导致抗病毒药物、疫苗和表达载体的合理设计。