Fowl adenovirus serotype 4-induced apoptosis, autophagy, and a severe inflammatory response in liver

Fowl adenovirus serotype 4 (FAdV-4) is a hepatotrophic virus that causes severe liver diseases. Upon histological examination, the most remarkable findings in the liver are small multifocal areas of necrosis and mononuclear cell infiltration, including basophilic intranuclear inclusion bodies in hepatocytes surrounded by a clear halo or which fill the entire nucleus. Here, we examined the mechanism responsible for FAdV-4-mediated hepatocyte damage in vivo and in vitro. The results showed that FAdV-4 impaired liver integrity and function, which decreased albumin and blood glucose concentrations and increased the plasma activity of aspartate aminotransferase and lactate dehydrogenase, compared with a non-infected control group (P < 0.05). FAdV-4 induced hepatocyte apoptosis in a time-dependent manner in vivo and in vitro. Additionally, we found that FAdV-4 also induced the autophagy of hepatocytes, which promoted the conversion of microtubule-associated protein light chain 3 (LC3-I) to LC3-II, which is a hallmarks of autophagy. Furthermore, the mRNA expressions of interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in vivo and in vitro showed a statistically significant increase (P < 0.05) compared to that of the control group. However, the molecular mechanisms underlying the FAdV-4 induced apoptotic and autophagic cell death remain unclear. In summation, our observations suggested that FAdV-4 induced liver injury via apoptosis, autophagy, and a severe inflammatory response.