Host Virus Interaction and Gene Expression

描述(申请人提供)：这项续期拨款申请的长期目标是了解人类副流感病毒3型(HPIV3)的宿主与病毒相互作用和基因表达的分子机制，HPIV3是一种重要的人类病原体，可攻击婴儿和儿童呼吸道的肺上皮细胞，导致急性毛细支气管炎、肺炎和哮喘。目前还没有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与病毒相互作用的过程，包括：(B)鉴定和表征上皮细胞的细胞表面受体(A)肌动蛋白结合蛋白、β-连环蛋白在HPIV3核糖核蛋白(RNP)复合体转录能力中的作用以及(C)HPIV3诱导的主要组织相容性复合体II的表达调控，这可能在导致感染相关的肺上皮损伤的细胞免疫中发挥重要作用。 我们还建议继续研究HPIV3RNA聚合酶L和P蛋白的结构和功能，特别是P蛋白的磷酸化作用以及L和P蛋白功能结构域的鉴定和鉴定。最后，我们希望利用我们实验室构建的HPIV3感染性基因的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对各种宿主-病毒相互作用途径有更深入的了解，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.