Gga-miR-30c-5p Enhances Apoptosis in Fowl Adenovirus Serotype 4-Infected Leghorn Male Hepatocellular Cells and Facilitates Viral Replication through Myeloid Cell Leukemia-1

• Published in: Viruses 2022-05, Vol.14 (5), p.990
• Main Authors: Haiyilati, Areayi, Zhou, Linyi, Li, Jiaxin, Li, Wei, Gao, Li, Cao, Hong, Wang, Yongqiang, Li, Xiaoqi, Zheng, Shijun J
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenoviridae - metabolism; Adenoviruses; Animals; Apoptosis; Biotechnology industry; Carcinoma, Hepatocellular; Caspase-3; Cell culture; chicken microRNA; Chickens; Cytochrome c; Ectopic expression; FAdV-4; Flow cytometry; gga-miR-30c-5p; Hepatitis; Infections; Leukemia; Liver Neoplasms; Male; Mcl-1; Mcl-1 protein; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Monoclonal antibodies; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Myeloid Cells - metabolism; Plasmids; Poultry; Proteins; Replication; RNA-mediated interference; Serogroup; Thermal cycling; Transfection; Virus Replication; Viruses
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14050990

Fowl adenovirus serotype 4 (FAdV-4) is the primary causative agent responsible for the hepatitis-hydropericardium syndrome (HHS) in chickens, leading to considerable economic losses to stakeholders. Although the pathogenesis of FAdV-4 infection has gained attention, the underlying molecular mechanism is still unknown. Here, we showed that the ectopic expression of gga-miR-30c-5p in leghorn male hepatocellular (LMH) cells enhanced apoptosis in FAdV-4-infected LMH cells by directly targeting the myeloid cell leukemia-1 (Mcl-1), facilitating viral replication. On the contrary, the inhibition of endogenous gga-miR-30c-5p markedly suppressed apoptosis and viral replication in LMH cells. Importantly, the overexpression of Mcl-1 inhibited gga-miR-30c-5p or FAdV-4-induced apoptosis in LMH cells, reducing FAdV-4 replication, while the knockdown of Mcl-1 by RNAi enhanced apoptosis in LMH cells. Furthermore, transfection of LMH cells with gga-miR-30c-5p mimics enhanced FAdV-4-induced apoptosis associated with increased cytochrome release and caspase-3 activation. Thus, gga-miR-30c-5p enhances FAdV-4-induced apoptosis by directly targeting Mcl-1, a cellular anti-apoptotic protein, facilitating FAdV-4 replication in host cells. These findings could help to unravel the mechanism of how a host responds against FAdV-4 infection at an RNA level.