禽呼肠孤病毒感染调控宿主miR-29a-3p与miR-200a-3p表达抑制细胞凋亡的分子机制

禽呼肠孤病毒（Avian reovirus, ARV）是危害养禽业的重要病原，其感染主要以关节炎/腱鞘炎、发育迟缓综合征等临床症状为特征。研究结果表明，ARV感染引起细胞凋亡导致组织损伤，然而对病毒感染引起细胞凋亡的调控分子机制还不十分清楚。我们在前期研究中发现，ARV感染引起宿主miRNAs的表达谱变化，其中miR-29a-3p和miR-200a-3p的表达显著上调，过表达两种miRNAs可抑制ARV诱导的细胞凋亡。本项目在此研究的基础上，通过分子生物学、分子病毒学和免疫学等技术手段，深入研究ARV感染调控miR-29a-3p与miR-200a-3p表达抑制细胞凋亡的分子机理，阐明病毒感染影响宿主miRNAs表达的分子基础，解析miRNAs抑制细胞凋亡的分子机制和对病毒复制的影响，在RNA水平上探索ARV的致病机理，为揭示ARV与宿主互作的致病机制和制定有效的防控措施提供依据。

Avian reovirus (ARV) is an important pathogenic agent endangering poultry industry. The ARV infection is mainly characterized by clinical symptoms such as arthritis/tenosynovitis and retarded development syndrome. Previous research results show that ARV infection induced apoptosis in host cells, leading to tissue damage in infected chickens. However, the molecular mechanism underlying ARV-induced apoptosis is still not very clear. Our data from previous studies indicate that ARV infection altered the expression profiles of host miRNAs, in which the expressions of mir-29a-3p and mir-200a-3p were significantly up-regulated, and overexpression of both miRNAs suppressed ARV-induced apoptosis. Thus, based on these findings, this project will be conducted to investigate into the molecular mechanisms underlying ARV-regulated expressions of miR-29a-3p and miR-200a-3p in host cells and suppression of apoptosis by the miRNAs using the tools in Molecular Biology, Molecular Virology and Immunology, to elucidate the molecular basis of ARV-mediated effect on miRNA expression and to unravel the molecular mechanism underlying suppression of apoptosis by ARV infection and its effect on virus replication. The results from this study will provide theoretical basis to uncover the pathogenesis of ARV-host interaction and help to formulate effective control measures for ARV infection.