The ATP synthase subunit β (ATP5B) is an entry factor for the hepatitis E virus

Ahmed, Zulfazal; Holla, Prasida; Ahmad, Imran; Jameel, Shahid

Hepatitis E occurs sporadically and as outbreaks due to contamination of drinking water. The causative agent, hepatitis E virus (HEV) is a hepatotropic non-enveloped RNA virus, which grows poorly in vitro. Consequently, many aspects of HEV biology are poorly characterized, including its cellular receptor and entry mechanism(s). Previous studies from our laboratory have shown that heparan sulfate proteoglycans (HSPGs) act as attachment factors for the virus. In the absence of purified high titer infectious virus, we have used hepatitis E virus-like particles (HEV-LPs) expressed and purified from E. coli to identify HEV entry factor(s) on liver cells in culture. Using a pull down and mass spectrometric approach, we identified the ATP synthase subunit β (ATP5B) to bind the HEV capsid protein. Its role in the entry of HEV was then validated using antibody and siRNA mediated approaches, and infectious HEV from the stools of a hepatitis E patient. Though ATP synthase is largely a mitochondrial protein, the cell surface expressed form of ATP5B is implicated in other viral infections.