Fig. 3: Mechanisms by which HAV counteracts innate immunity.
From: Redefining the immune landscape of hepatitis A virus infection
A schematic representation of the strategies by which HAV reportedly interferes with innate immunity. a The cysteine protease HAV 3Cpro undergoes sequential autoprocessing of the P3 polyprotein precursor—involving sequential liberation into single intermediates, starting with 3ABCD, followed by 3ABC and 3CD and finally 3C. The protein 2B is also depicted for its role in counteracting innate immunity. b The 3CD reportedly cleaves TRIF, the adapter protein mediating TLR3 signaling (1). The 3ABCpro intermediate cleaves MAVS (2). NEMO is a target of direct cleavage by 3Cpro (3). The nonstructural HAV protein 2B is believed to interact with MAVS, disrupting the activity of TBK1 and IKKε kinases, although the precise mechanism is unclear (4). Recent studies show that HAV infection increases the expression of microRNA hsa-miR-146a-5p, which targets and degrades TRAF6 mRNA (5).
