Hepatitis B virus and hepatitis C virus interaction in Huh-7 cells☆

Background/Aims

Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) increases the risk of development and the severity of chronic liver disease. Although dominant and suppressive effects of each virus over the other have been reported in vivo, in vitro studies of HBV/HCV co-infection have been limited to analysis of the effects of over-expression of HCV proteins on HBV replication.

Methods

We have re-examined HBV/HCV interactions in Huh-7 cells following co-infection with cell culture-propagated HCV (HCVcc; genotype 2a) and a recombinant adenovirus vector capable of delivering a replication-competent HBV genome (AdHBV; genotype A).

Results

While intracellular HCV RNA levels were significantly increased when cells were pre-infected with AdHBV, HCV replication and virion secretion were not altered by simultaneous infection with AdHBV or AdHBV superinfection of HCV-infected cells. Likewise intracellular and secreted HBV DNA levels and HBV promoter activities were either unchanged or modestly increased by HCVcc infection. Despite this, HCV E2 and HBsAg proteins colocalized extensively in co-infected cells suggesting shared stages in viral egress.

Conclusions

These studies indicate that there is little direct interaction of HBV and HCV in co-infected hepatocytes and imply that indirect effects of host-viral interactions dictate viral dominance in HBV/HCV co-infected individuals.

Abbreviations: HCV, hepatitis C virus, HBV, hepatitis B virus, GFP, green fluorescent protein, HBsAg, hepatitis B virus surface antigen, HBcAg, hepatitis B virus core antigen, ER, endoplasmic reticulum, HCVcc, cell-culture propagated HCV, HCVpp, HCV pseudoparticles

Keywords: HBV, HCV, Co-infection, Superinfection, Hepatocytes, Pathogenesis