Investigation of Mitochondrial and Peroxisomal Morphology and IFN response Changes by Hepatitis B Virus

Abstract

Interferons (IFNs) treatment is used to cure chronic hepatitis B patients despite its limited efficacy. However, IFNα treatment causes a few of side effects. Thus, type III IFN is suggested to substitute the type I IFNs because of its low adverse effects. Mitochondria and peroxisomes are the main platforms of antiviral signaling to produce IFNs through Rig-I-like receptors (RLRs) and mitochondrial antiviral signaling protein (MAVS) mediated pathway. RLRs pathway that mediates mitochondrial MAVS is known to produce both type I IFNs and type III IFNS but peroxisomal MAVS mainly contributes to type III IFN production. HBV infection suppresses the type I IFN responses of host cells by its evasion strategies that degrade MAVS expressed on mitochondria. Additionally, type I IFN response of HBV infected cells become abnormal by increased fission of mitochondria that leads to mitophagy. However, it is unclear how HBV affects to type III IFN production pathway. Furthermore, the effects of peroxisomal morphology change on the innate immune responses is still not identified even a few of reports showed the modified peroxisomal biogenesis during viral infections. In this study, the effects of HBV on the expression of IFNs mRNA and the morphology of mitochondria and peroxisome were observed. Highly increased expression level of type III IFN by poly(I:C) transfection was measured in HepG2.2.15 while the type I IFN production was suppressed. And the modified morphology of peroxisomes and mitochondria are observed in both HepG2.2.15 and HBV infected NTCP expressing HepG2. Although the direct interaction between the morphology change of peroxisome and IFN response was not revealed, the connections between the two observations were suggested.