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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Taylor & Francis Group
2025-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2025.2525269 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sarah Schlienkamp |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2fa5be7b0b664d7a847c25567d8d7a80 |
| institution | Matheson Library |
| issn | 2222-1751 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-2fa5be7b0b664d7a847c25567d8d7a802025-07-16T11:29:23ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2525269Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture modelsSarah Schlienkamp0Olinda Pinto Veiga1André Gömer2Luca Nörthemann3Leyla Sirkinti4Nicola Frericks5Kathrin Sutter6Florian W. R. Vondran7Axel Hamprecht8Daniel Todt9Eike Steinmann10Volker Kinast11Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, GermanyInstitute for Medical Microbiology and Virology, Carl von Ossietzky University Oldenburg, Oldenburg, GermanyDepartment of Molecular and Medical Virology, Ruhr University Bochum, Bochum, GermanyDepartment of Molecular and Medical Virology, Ruhr University Bochum, Bochum, GermanyDepartment of Molecular and Medical Virology, Ruhr University Bochum, Bochum, GermanyDepartment of Molecular and Medical Virology, Ruhr University Bochum, Bochum, GermanyInstitute for Virology, University Hospital Essen, Essen, GermanyDepartment of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, GermanyInstitute for Medical Microbiology and Virology, Carl von Ossietzky University Oldenburg, Oldenburg, GermanyDepartment of Molecular and Medical Virology, Ruhr University Bochum, Bochum, GermanyDepartment of Molecular and Medical Virology, Ruhr University Bochum, Bochum, GermanyInstitute for Medical Microbiology and Virology, Carl von Ossietzky University Oldenburg, Oldenburg, GermanyHepatitis 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.https://www.tandfonline.com/doi/10.1080/22221751.2025.2525269Hepatitis E virusinnate immunityzoonosiscell culture modelsnatural hostpigs |
| spellingShingle | 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 Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture models Emerging Microbes and Infections Hepatitis E virus innate immunity zoonosis cell culture models natural host pigs |
| title | Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture models |
| title_full | Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture models |
| title_fullStr | Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture models |
| title_full_unstemmed | Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture models |
| title_short | Interferon-induced immune signatures are associated with suppression of HEV infection in porcine cell culture models |
| title_sort | interferon induced immune signatures are associated with suppression of hev infection in porcine cell culture models |
| topic | Hepatitis E virus innate immunity zoonosis cell culture models natural host pigs |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2025.2525269 |
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