Key result
Hepatitis A virus 3C protease cleaves NEMO to block IFN-β synthesis for immune evasion.
HAV 3C protease cleaves NEMO to evade the host immune response by impairing IFN-β synthesis.
No immediate clinical implications for HAV; leaves open whether 3C protease targeting could restore IFN responses in humans.
NEMO (NF-κB essential modulator) is a bridging adaptor indispensable for viral activation of interferon (IFN) antiviral response. Herein, we show that hepatitis A virus (HAV) 3C protease (3Cpro) cleaves NEMO at the Q304 residue, negating its signaling adaptor function and abrogating viral induction of IFN-β synthesis via the retinoic acid-inducible gene I/melanoma differentiation-associated protein 5 (RIG-I/MDA5) and Toll-like receptor 3 (TLR3) pathways. NEMO cleavage and IFN antagonism, however, were lost upon ablation of the catalytic activity of 3Cpro. These data describe a novel immune evasion mechanism of HAV.
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Wang et al. (2014) studied Hepatitis A Virus infection. Hepatitis A virus 3C protease (3Cpro) vs. Catalytically inactive 3Cpro was evaluated on NEMO cleavage and IFN-β synthesis induction. Hepatitis A virus 3C protease cleaves NEMO at the Q304 residue, abrogating viral induction of IFN-β synthesis and revealing a novel immune evasion mechanism.
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