College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, People's Republic of China.
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, People's Republic of China.
Poult Sci. 2022 Jul;101(7):101941. doi: 10.1016/j.psj.2022.101941. Epub 2022 May 4.
Fowl adenovirus serotype 4 (FAdV-4), the predominant causative agent of hepatitis-hydropericardium syndrome (HHS), has caused severe economic losses to poultry industry since 2015. Although fiber2 and hexon have been confirmed to be the virulence-related factors, the roles of nonstructural viral proteins in pathogenicity of FAdV-4 remain poorly understood. Here, a tandem mass spectrometry (MS) was used to identify host factors interacted with 100K protein of hypervirulent FAdV-4 isolate (CH/HNJZ/2015), and 2595 cellular proteins associated with many biological processes and pathways were identified according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Among the proteins, HSC70 was verified to interact with 100K through co-immunoprecipitation assay. Notably, overexpression of HSC70 promoted the replication of FAdV-4 in LMH cells, whereas blocking HSC70 with inhibitor ver-155008 markedly suppressed viral replication. Collectively, these findings suggested that many cellular proteins involved in FAdV-4 infection through interacting with 100K and HSC70 positively regulated virus replication.
禽腺病毒血清型 4（FAdV-4）是导致肝炎-心包积水综合征（HHS）的主要病原体，自 2015 年以来给家禽养殖业造成了严重的经济损失。虽然纤维 2 和六邻体已被证实是与毒力相关的因素，但非结构病毒蛋白在 FAdV-4 致病机制中的作用仍知之甚少。在这里，串联质谱（MS）被用于鉴定与高致病性 FAdV-4 分离株（CH/HNJZ/2015）100K 蛋白相互作用的宿主因子，根据基因本体论和京都基因与基因组百科全书通路分析，共鉴定出与许多生物过程和通路相关的 2595 种细胞蛋白。在这些蛋白中，通过免疫共沉淀实验验证了 HSC70 与 100K 相互作用。值得注意的是，HSC70 的过表达促进了 FAdV-4 在 LMH 细胞中的复制，而用抑制剂 ver-155008 阻断 HSC70 则显著抑制了病毒的复制。总之，这些发现表明，许多参与 FAdV-4 感染的细胞蛋白通过与 100K 和 HSC70 的相互作用，正向调节病毒的复制。
