Suppression of IFN-ß induction by proteins of the hepatitis A virus, especially by the HAV/2B protein

Hepatitis A virus antagonizes the innate immune response by inhibition of IRF-3 activation which results in efficient suppression of interferon-β synthesis. This study showed that this ability of the virus is mediated by the viral non-structural proteins 2B and 3ABC. While the processing intermediate 3ABC targets MAVS, 2B might interfere with IRF-3 activation in an indirect manner by associating with intracellular membranes. Deletion of the C-terminal transmembrane domain of 2B results in a loss of function concerning the suppression of IRF 3 activation. In addition to suppression of IRF-3 activation, HAV partially down regulates protein expression which is mediated by the viral non-structural protein 2C. This function of 2C probably depends on its membrane association, too. In the second part of this work could be shown that the suppression of IRF-3 activation and down regulation of protein expression is not due to an adaptation of HAV to growth in cultivated cells because proteins of wildtype viruses show these properties also. These results imply that HAV is able to inhibit IRF-3 activation and partially down regulates protein expression in vivo