Host Virus Interaction and Gene Expression

描述（由申请人提供）：本更新授权申请的长期目标是了解3型人副流感病毒（HPIV 3）的宿主-病毒相互作用和基因表达的分子机制，HPIV 3是一种重要的人类病原体，靶向婴儿和儿童呼吸道的肺上皮细胞，导致急性细支气管炎、肺炎和哮吼。有效的疫苗或抗病毒药物，以打击HPIV 3感染目前是不可用的。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，包括：（B）上皮细胞的细胞表面受体的鉴定和表征（a）肌动蛋白结合蛋白的作用，β连环蛋白在HPIV 3核糖核蛋白（RNP）复合物的转录能力中的作用，以及（c）HPIV 3诱导的主要组织相容性复合物II表达的调节，其可能在导致肺上皮感染相关损伤的细胞免疫中起重要作用。 我们还建议继续我们的研究，了解HPIV 3的RNA聚合酶，L和P蛋白的结构和功能，特别是关于P蛋白磷酸化的作用和L和P蛋白的功能结构域的鉴定和表征。最后，我们希望利用反向遗传学的感染性cDNA HPIV 3在我们的实验室构建的一些独特的顺式调节突变体的表型特征进行研究。 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，最终可能导致抗病毒药物，疫苗和表达载体的合理设计。

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.