MOLECULAR BASIS FOR PARAINFLUENZA 3 INFECTION

描述：人副流感病毒3型（HPF3）， 非节段负链RNA病毒的副粘病毒家族，是一种 儿童下呼吸道疾病重要病原体及病因 几种最重要的儿童病毒性疾病（哮吼， 细支气管炎和肺炎）。 对HPF3引起的感染的认识 在美国，由于越来越多的人 潜在的免疫缺陷和严重的HPF3疾病正在重新出现。 目前没有治疗方法或疫苗可以对抗这种情况 严重的儿科病原体，在知识方面仍然存在空白， 导致病毒生长的基本过程。 莫斯科纳博士的研究 提供了对控制病毒宿主细胞的一些因素的理解 HPF3的相互作用，包括HN在病毒诱导的融合中的作用 过程 目前提案的总体目标是扩大 研究HPF3的分子发病机制。 核心假设 包膜糖蛋白血凝素-神经氨酸酶（HN）受体 相互作用对病毒生命的几个基本组成部分至关重要 循环--进入、融合和释放--这种相互作用调节着 体外和体内的致病性。 当前的具体目标 主要内容如下：（1）阐明病毒HN蛋白和细胞受体 病毒-宿主相互作用的组分，具体地通过（A）评估病毒-宿主相互作用的组分， 使用HPF3 HN变体，HN在病毒进入、融合和释放中的作用， 在受体结合或融合促进方面改变，以及（B）鉴定 HN的功能性细胞受体分子。 (2)评估战略 干扰HN-受体相互作用，从而验证假设 关于HN在病毒生命周期中的功能，使用（A）唾液酸 模拟HN受体糖部分的类似物作为诱饵， 干扰病毒附着和（B）HN在表面上的表达 未感染的细胞来模拟病毒干扰，从而防止病毒进入。 (3)为了分析HN-受体相互作用对 通过将研究扩展到HPF3感染， 棉鼠，一种模拟HPF3下呼吸道感染的模型， 伙计 她将检验以下假设：（A）病毒受体的亲和力 相互作用是肺发病机制的决定因素，（B） 神经氨酸酶决定了肺部感染的结果， 细胞培养

DESCRIPTION: Human parainfluenza virus type 3 (HPF3), a member of the paramyxovirus family of non-segmented negative-strand RNA viruses, is an important agent of lower respiratory tract disease in children and causes several of the most significant childhood viral diseases (croup, bronchiolitis and pneumonia). The recognition of infections caused by HPF3 is increasing in the U.S. due to the increasing numbers of individuals with underlying immune deficiencies, and serious HPF3 disease is re-emerging. There are currently no treatments or vaccines available to combat this serious pediatric pathogen, and there remain gaps in the knowledge of fundamental processes leading to growth of the virus. Dr. Moscona's studies have provided an understanding of some factors controlling virus-host cell interactions for HPF3, including the role of HN in the virus-induced fusion process. The overall goal of the current proposal is to expand the investigation of the molecular pathogenesis of HPF3. The central hypothesis is that the envelope glycoprotein hemagglutinin-neuraminidase (HN)-receptor interaction is critical for several essential components of the viral life cycle -- entry, fusion and release -- and that this interaction regulates pathogenicity in vitro and in vivo. The specific objectives of the current proposal are: (1) To elucidate both the viral HN and cellular receptor components of the virus-host interaction, specifically by (A) evaluating the role of HN in viral entry, fusion and release using HPF3 HN variants that are altered in receptor binding or fusion promotion and (B) identifying functional cellular receptor molecules for HN. (2) To evaluate strategies for interfering with HN-receptor interaction and thus test the hypothesis about the functions of HN in the viral life cycle, using (A) sialic acid analogs that mimic the sugar moiety of the HN receptor as decoys to interfere with viral attachment and (B) HN expression on the surface of uninfected cells to mimic viral interference and thus prevent viral entry. (3) To analyze the contribution of the HN-receptor interaction to pathogenesis in vivo by extending the studies to HPF3 infection in the cotton rat, a model that mimics HPF3 lower respiratory tract infection in man. She will test the hypotheses that (A) avidity of virus-receptor interaction is a determinant of pathogenesis in the lung and (B) neuraminidase determines the outcome of infection in the lung as it does in cell culture.