禽腺病毒4型（FAdV-4）感染导致的禽肝炎-心包积液综合征是严重危害我国养禽业的新发传染病。前期研究发现，宿主因子热休克同源蛋白HSC70与FAdV-4的100K蛋白相互作用，过表达HSC70可促进FAdV-4的复制。因此，研究两者相互作用影响病毒复制的分子机制对于阐明FAdV-4的致病机理具有重要意义。本项目首先通过免疫共沉淀技术明确两者互作关键区域；随后利用反向遗传操作技术、CRISPR/Cas9技术和慢病毒包装技术，分别从病毒层面和宿主层面明确两者互作对病毒复制的影响；最后确定HSC70通过与100K蛋白相互作用调控病毒复制的具体阶段，阐明其发挥作用的分子机制。项目将深化对FAdV-4感染过程的认识，并为病毒致病机理的解析提供理论基础。

Hepatitis-hydropericardium syndrome caused by fowl adenovirus 4 (FAdV-4) infection is a newly emerging poultry infectious disease, resulting in devastating economic losses to poultry industry in China. Our previous study demonstrated that host factor HSC70 interacted with FAdV-4 100K protein and overexpression of HSC70 promoted FAdV-4 replication. Therefore, further investigating the underlying mechanism of HSC70 regulating FAdV-4 replication through interacting with 100K protein will contribute to elucidate the pathogenesis of FAdV-4. In this proposal, the key domains involved in the interaction between 100K protein and HSC70 will be investigated by co-immunoprecipitation firstly. Secondly, the regulatory effect of 100K protein and HSC70 interaction on FAdV-4 replication will be determined by reverse genetic technology, CRSPR/Cas9 and lentiviral expression and packaging system from the perspective of virus and host, respectively. Finally, the underlying molecular mechanism of HSC70 regulating FAdV-4 replication will be analyzed by studying its influence on the exact replicative phase. This study will deepen the understanding of FAdV-4 infection and provide theoretical foundation for elucidating the pathogenesis of FAdV-4.