Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture models

Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture models

Hepatitis E virus genotype 3 (HEV-3) is a zoonotic pathogen with pigs representing the natural host. Although HEV-3 infections in humans are often self-limiting, severe or chronic cases can occur. In contrast, HEV-3 infections in pigs, the primary reservoir, remain asymptomatic. To assess the initia...

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Main Authors: Sarah Schlienkamp, Olinda Pinto Veiga, André Gömer, Luca Nörthemann, Leyla Sirkinti, Nicola Frericks, Kathrin Sutter, Florian W. R. Vondran, Axel Hamprecht, Daniel Todt, Eike Steinmann, Volker Kinast
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Emerging Microbes and Infections
Subjects:
Hepatitis E virus
innate immunity
zoonosis
cell culture models
natural host
pigs
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2025.2525269
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Summary:Hepatitis E virus genotype 3 (HEV-3) is a zoonotic pathogen with pigs representing the natural host. Although HEV-3 infections in humans are often self-limiting, severe or chronic cases can occur. In contrast, HEV-3 infections in pigs, the primary reservoir, remain asymptomatic. To assess the initial transcriptional response in porcine cells during HEV-3 infection and pave the way for mechanistic studies of species-specific virus–host interactions, we aimed to establish porcine cell culture models, including primary porcine hepatocytes (PPHs) and porcine cell lines. PPHs supported the full HEV-3 replication cycle while intrinsic immunity, driven by the interferon-stimulated gene (ISG) system, played a central role in restricting viral replication. JAK inhibition enhanced viral replication and suppressed ISG expression, highlighting the importance of IFN signalling in antiviral defense. Transcriptional profiling revealed a global modulation of host responses upon HEV infection, including pathways linked to immunity, inflammation, and metabolism. Porcine cell lines were permissive to HEV infection and treatment with recombinant porcine IFN-α subtypes induced a robust ISG response and effectively inhibited HEV replication in a dose-dependent manner. These findings establish porcine hepatocytes and cell lines as valuable tools to study HEV-host interactions, demonstrating the critical role of IFN-mediated intrinsic immunity in HEV restriction and highlighting subtype-specific antiviral effects of porcine IFN-α.
ISSN:2222-1751

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