Host Virus Interaction and Gene Expression

描述（由申请人提供）：该续期拨款申请的长期目标是了解宿主-病毒相互作用的分子机制和人类副流感病毒3型（HPIV3）的基因表达，HPIV3是一种重要的人类病原体，可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，肺炎和群。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-病毒相互作用过程，包括(b)上皮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 - catenin在HPIV3核糖核蛋白（RNP）复合物转录能力中的作用，以及(c) HPIV3诱导的主要组织相容性复合物II的表达调控，这可能在导致感染相关肺上皮损伤的细胞免疫中发挥重要作用。

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.