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

Abstract

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 c 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.

Role of microRNAs in host defense against porcine reproductive and respiratory syndrome virus infection: a hidden front line

“…miR-30c is found to impair the IFN-I signaling by targeting the 3’ UTR of IFNAR2 and JAK1, ultimately promoting the replication of PRRSV ( Figure 2B , Table 1 ) ( 107 , 108 ). In addition to PRRSV, gga-miR-30c-5p also can facilitated the replication of fowl adenovirus serotype 4 by directly targeting myeloid cell leukemia-1 ( 109 ). Avian reovirus (ARV) significantly upregulates the gga-miR-30c-5p expression, and gga-miR-30c-5p can inhibit the ARV-induced autophagy by targeting autophagy related 5, thereby suppressing ARV proliferation ( 110 ).…”

Biological features of fowl adenovirus serotype-4

“…To dissect the roles of miRNAs in host, RNA sequencing was performed in LMH cells infected with FAdV-4 ( Haiyilati et al., 2022 ). During this study it was found that the expression of 552 miRNAs in were altered.…”