猪繁殖与呼吸综合征病毒ORF1b影响其致病性的分子机制

项目名称： 猪繁殖与呼吸综合征病毒ORF1b影响其致病性的分子机制

项目编号： No.31330077

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 水产学、兽医学

项目作者： 杨汉春

作者单位： 中国农业大学

项目金额： 297万元

中文摘要： 猪繁殖与呼吸综合征是由猪繁殖与呼吸综合征病毒（PRRSV）引起的以母猪繁殖障碍和各生长阶段猪的呼吸道疾病为特征的病毒性疫病。本项目以我国PRRSV毒株为材料，开展ORF1b编码的非结构蛋白影响PRRSV致病性的分子机制研究。在利用反向遗传操作技术，分别构建PRRSV高致病性和低致病性毒株的非结构蛋白Nsp9、Nsp10、Nsp11、Nsp12基因相互置换的嵌合病毒的基础上，研究ORF1b编码的非结构蛋白对PRRSV增殖和组织嗜性的影响及其分子机制，分析ORF1b编码的非结构蛋白在PRRSV诱导宿主细胞自噬和凋亡中的作用及其分子机制，以期揭示PRRSV增殖能力、组织嗜性与致病性间的相互关系，解析其诱导宿主细胞自噬和凋亡与病毒增殖及致病性的关系，发现对PRRSV致病性具有决定作用的非结构蛋白及其影响的分子机制，为阐释我国PRRSV高致病性毒株致病性增强的机理提供科学依据。

中文关键词： 猪繁殖与呼吸综合征病毒;开放阅读框1b;致病性;致病机制;分子机制

英文摘要： Porcine reproductive and respiratory syndrome is a viral disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), which is characterized by reproductive failure in sows, and respiratory conditions in pigs of all ages. This project will focus on molecular pathogenesis involved by ORF1b of PRRSV using Chinese strains of PRRSV. On the basis of construction of chimeric viruses with exchange of Nsp9, Nsp10, Nsp11 and Nsp12 genes between the highly and low pathogenic PRRSV strains by means of reverse genetic manipulation, we explore the effect of nonstructural proteins encoded by ORF1b on the growth and tissue tropism of PRRSV and its molecular mechanism, and analyze the role of nonstructural proteins encoded by ORF1b in the induction of target cells autophagy and apoptosis and its molecular mechanism. The aims of our studies are to reveal the relationships between the growth ability, tissue tropism and pathogenicity of PRRSV, and between the autophagy and apoptosis induced by PRRSV and its growth and pathogenicity, and finally explore the nonstructural protein for determining the pathogenicity of PRRSV and the molecular pathogenesis involved by ORF1b of PRRSV. The data obtained by this project will provide scientific evidence for addressing the mechanism associated with the pathogenicity enhancement of the highly pathogenic PRRSV emerging in China.

英文关键词： PRRSV;ORF1b;pathogenicity;pathogenesis;molecular mechanism