Fowl adenovirus serotype 4 uses gga-miR-181a-5p expression to facilitate viral replication via targeting of STING

Fowl adenovirus serotype 4 (FAdV-4) has caused substantial economic losses to the poultry industry and it has become a serious pathogen of poultry in China since 2015. MicroRNAs (miRNAs) play vital roles in regulating viral infection. However, how miRNAs regulate FAdV-4 replication in Leghorn male hepatocellular (LMH) cells remains unclear. This study aimed to elucidate the role of gga-miR-181a-5p in regulating FAdV-4 replication. The findings indicated that the expression of gga-miR-181a-5p was significantly upregulated in LMH cells during FAdV-4 infection. Also, the transfection of gga-miR-181a-5p mimics promoted FAdV-4 replication, while the opposite result was observed when gga-miR-181a-5p inhibitor was transfected in LMH cells. Moreover, the stimulator of interferon genes (STING) was found to be the target gene of gga-miR-181a-5p using software analysis, further confirming that STING was the target of gga-miR-181a-5p and gga-miR-181a-5p could negatively regulate the expression of STING at the mRNA and protein levels. Finally, the results showed that the overexpression of STING inhibited FAdV-4 replication and the knockout of STING promoted FAdV-4 replication. The collective findings revealed a novel host evasion mechanism adopted by FAdV-4 via gga-miR-181a-5p, suggesting novel strategies for designing miRNA-based vaccines and therapies.