Apoptotic cell death in an animal model of virus-induced acute liver failure – observations during Lagovirus europaeus/GI.2 infection

Abstract

Abstract Lagovirus europaeus/GI.2 causes severe and highly fatal Rabbit Haemorrhagic Disease. Because of its characteristics, this infection is used as an animal model for acute liver failure (ALF). Apoptosis is one of the key processes underlying ALF and has been described as one of the mechanisms of RHD pathogenesis. Apoptotic cell death has been quite well characterized in infection with different variants of GI.1 strains, but so far GI.2 genotype has not been widely studied. In this study, we performed an evaluation of apoptotic cell death in hepatocytes of rabbits infected with Lagovirus europaeus/GI.2. We analyzed the expression of genes involved in apoptotic cell death by real-time PCR and performed immunohistochemical (IHC) assay. As a result, we showed a significant increase in the expression of caspase-3 and the pro-apoptotic Bax and anti-apoptotic Bcl-2 in infected animals. In addition, we recorded increased Bax/Bcl2 ratios. IHC analysis showed the presence of morphological signs of apoptosis in the hepatocytes of infected rabbits. Our results indicate that caspase-3 and the proteins from Bcl2 families play a key role in apoptosis induced by Lagovirus europaeus/GI.2 infection.