Limited impact of hepatitis A virus 3C protease-mediated cleavage on the functions of NEMO in human hepatocytes.

ABSTRACT: NF-κB essential modulator (NEMO) is critically involved in the induction of interferons (IFNs) and pro-inflammatory cytokines. Hepatitis A virus (HAV) 3C protease was recently identified to cleave NEMO in non-hepatic cells. This study aimed at understanding efficiency and function of HAV 3C-mediated NEMO cleavage in hepatocytes. HAV 3C protease and its precursor 3CD strongly affected NEMO abundance in ectopic expression models, which was not observed in HAV replicon cells and upon HAV infection. Using a cleavage-resistant NEMO mutant, we found that specific cleavage by 3C only marginally contributed to NEMO degradation, whereas the magnitude of the effect was due to cytotoxic effects induced by 3C activity. Cleavage efficiency generally did not suffice to disrupt the type I IFN or NF-κB si

SUBMITTER: Huang H-E 

PROVIDER: S-EPMC11852894 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature