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The hepatitis E virus capsid protein ORF2 counteracts cell-intrinsic antiviral responses to enable persistence in hepatocytes

GSE288400 Homo sapiens Expression profiling by high throughput sequencing 5 samples Submitted 2025/09/04 Platform GPL21697
Summary
We used scRNA-seq to study the cell-intrinsic antiviral response to hepatitis E virus infection in the immunocompetent hepatoma cell line HepG2/C3A. In this study, we identified a replication-limiting bottleneck at approximately 56 h post-infection at which the presence of the viral capsid protein ORF2 is decisive for establishment of an equilibrium between viral replication and the antiviral response. ORF2 antagonizes antiviral signaling downstream of pattern recognition receptors, at least partly through direct interaction with the central adaptor protein TBK1. By scRNA-seq, we confirmed that ORF2 dampens the antiviral response directly within infected cells, thereby also affecting the antiviral response in uninfected bystanders. In the presence of ORF2, the antiviral response was globally dampened at the early, replication-limiting bottleneck. This further substantiated that the equlibirium between viral replication and the antiviral response is a crucial mechanism of HEV persistence in hepatocytes.
Published in
The hepatitis E virus capsid protein ORF2 counteracts cell-intrinsic antiviral responses to enable persistent replication in cell culture
Mehnert AK, Stegmaier S, Ramirez Alvarez C et al. · PLoS pathogens 2025 · PMID 40982567 · doi:10.1371/journal.ppat.1013516
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Also filed as BioProject PRJNA1217379 and SRA study SRP560726. Searching any of these in the dataset finder brings you back here.

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