Hepatitis viruses and the MAPK pathway: is this a survival strategy?

The viruses that cause hepatitis comprise of at least five different agents, which share the ability to cause inflammation and necrosis of the liver. The disease spectrum is quite diverse and the outcome of infection by the different hepatitis viruses can be rationalized based on virus-host cell interactions. New insights into the molecular basis of viral hepatitis reveal that three of these agents - the hepatitis B, C and E viruses (HBV, HCV and HEV) modulate the mitogen-activated protein kinase (MAPK) signaling pathway. In this review we briefly describe the structural organization of the MAPK cascade and emphasize its importance as a central pathway in the signaling network. Selected mechanisms through which HBV, HCV and HEV proteins target various steps in the MAPK pathway are discussed and used to propose a pro-survival outcome for the host cell. In addition, we offer an insight into how the common theme of MAPK activation and its downstream effects may be used to rationalize the different outcomes of hepatitis B, C and E.