The hepatitis E virus capsid protein ORF2 counteracts cell-intrinsic antiviral responses to enable persistent replication in cell culture.

ABSTRACT: Hepatitis E virus (HEV) is a significant human pathogen causing both acute and chronic infections worldwide. The cell-intrinsic antiviral response serves as the initial defense against viruses and has been shown to be activated upon HEV infection. HEV can replicate in the presence of this response, but the underlying mechanisms remain poorly understood. Here, we investigated the roles of the structural proteins ORF2 and ORF3 in the cell-intrinsic antiviral response to HEV infection. Mechanistically, we validated that ectopic ORF2, but not ORF3, interfered with antiviral and inflammatory signaling downstream of pattern recognition receptors, in part through interaction with the central adaptor protein TANK binding kinase 1. In the full-length viral context, ORF2 contributed to a reduced ant

SUBMITTER: Mehnert AK 

PROVIDER: S-EPMC12478880 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature