THREE DIMENSIONAL STRUCTURE OF PARMYOVIRUS HN

副粘病毒是导致儿童呼吸道疾病的最重要原因。我们研究的长期目标是开发预防副流感病毒(PIV)引起的呼吸道疾病的方法。为了达到这一目标，拟议的研究将集中在利用X射线结晶学建立副粘病毒HN蛋白的三维结构(3D)。这种蛋白在病毒附着、渗透、病毒传播中的作用，以及作为主要的中和抗原，使其结构对疫苗和药物开发具有重要意义。利用反向遗传学，这一建议还解决了PIV宿主范围和组织趋向性的决定因素。利用遗传和生化方法，AIMS 3探索了PIV萌芽的未知机制，这是药物干预的潜在目标。本方案的具体目标是：1)方案：建立HN的高分辨率3D结构。2)问题：副流感病毒宿主范围和组织嗜性的病毒特异性决定因素是什么？3)建议：确定副粘病毒膜蛋白诱导病毒萌发的机制。HN结构、病毒释放(萌芽)和病毒传播(宿主范围决定因素)是感染周期中潜在的干预目标。

Paramyxoviruses are the most important cause of respiratory disease in children. The long-term objectives of our research are to develop means to prevent respiratory disease caused by parainfluenza viruses (PIV). To reach that objective, the proposed research will focus on establishing the three- dimensional structure (3D) of the paramyxovirus HN protein using x-ray crystallography. The role of this protein in virus attachment, penetration, virus spread, and as a major neutralizing antigen makes the structure important for vaccine and drug development. Using a reverse genetics, this proposal also addresses the determinants of PIV host range and tissue tropism. Using genetic and biochemical approaches aims 3 explores the unknown mechanism of PIV budding, a potential target for drug intervention. The specific aims of this proposal are 1) Proposal: Establish a high-resolution 3D structure of HN. 2) Question: What are the virus specific determinants of parainfluenza host range and tissue tropism? 3) Proposal: determine the mechanism of virus budding induced by paramyxovirus membrane proteins. The studies proposed in these aims, HN structure, virus release (budding), and virus spread (host range determinants) are potential intervention targets in the infectious cycle.