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Interferon-Stimulated Gene 15 Knockout in Mice Impairs IFNα-Mediated Antiviral Activity

Type I interferon (IFN) plays an important role in the host defense against viral infection by inducing expression of interferon-stimulated genes (ISGs). In a previous study, we found that porcine interferon-stimulated gene 15 (ISG15) exhibited antiviral activity against PRV in vitro. To further inv...

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Autores principales: Li, Chen, He, Wen-Feng, Li, Long-Xi, Chen, Jing, Yang, Guo-Qing, Chang, Hong-Tao, Liu, Hui-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502845/
https://www.ncbi.nlm.nih.gov/pubmed/36146669
http://dx.doi.org/10.3390/v14091862
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author Li, Chen
He, Wen-Feng
Li, Long-Xi
Chen, Jing
Yang, Guo-Qing
Chang, Hong-Tao
Liu, Hui-Min
author_facet Li, Chen
He, Wen-Feng
Li, Long-Xi
Chen, Jing
Yang, Guo-Qing
Chang, Hong-Tao
Liu, Hui-Min
author_sort Li, Chen
collection PubMed
description Type I interferon (IFN) plays an important role in the host defense against viral infection by inducing expression of interferon-stimulated genes (ISGs). In a previous study, we found that porcine interferon-stimulated gene 15 (ISG15) exhibited antiviral activity against PRV in vitro. To further investigate the antiviral function of ISG15 in vivo, we utilized ISG15 knockout (ISG15(-/-)) mice in this study. Here, we demonstrate that ISG15(-/-) mice were highly susceptible to PRV infection in vivo, as evidenced by a considerably reduced survival rate, enhanced viral replication and severe pathological lesions. However, we observed no significant difference between female and male infected WT and ISG15(-/-) mice. Moreover, ISG15(-/-) mice displayed attenuated antiviral protection as a result of considerably reduced expression of IFNβ and relevant ISGs during PRV replication. Furthermore, excessive production of proinflammatory cytokines may be closely related to encephalitis and pneumonia. In further studies, we found that the enhanced sensitivity to PRV infection in ISG15(-/-) mice might be caused by reduced phosphorylation of STAT1 and STAT2, thereby inhibiting type I IFN-mediated antiviral activity. Based on these findings, we conclude that ISG15 is essential for host type I IFN-mediated antiviral response.
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spelling pubmed-95028452022-09-24 Interferon-Stimulated Gene 15 Knockout in Mice Impairs IFNα-Mediated Antiviral Activity Li, Chen He, Wen-Feng Li, Long-Xi Chen, Jing Yang, Guo-Qing Chang, Hong-Tao Liu, Hui-Min Viruses Article Type I interferon (IFN) plays an important role in the host defense against viral infection by inducing expression of interferon-stimulated genes (ISGs). In a previous study, we found that porcine interferon-stimulated gene 15 (ISG15) exhibited antiviral activity against PRV in vitro. To further investigate the antiviral function of ISG15 in vivo, we utilized ISG15 knockout (ISG15(-/-)) mice in this study. Here, we demonstrate that ISG15(-/-) mice were highly susceptible to PRV infection in vivo, as evidenced by a considerably reduced survival rate, enhanced viral replication and severe pathological lesions. However, we observed no significant difference between female and male infected WT and ISG15(-/-) mice. Moreover, ISG15(-/-) mice displayed attenuated antiviral protection as a result of considerably reduced expression of IFNβ and relevant ISGs during PRV replication. Furthermore, excessive production of proinflammatory cytokines may be closely related to encephalitis and pneumonia. In further studies, we found that the enhanced sensitivity to PRV infection in ISG15(-/-) mice might be caused by reduced phosphorylation of STAT1 and STAT2, thereby inhibiting type I IFN-mediated antiviral activity. Based on these findings, we conclude that ISG15 is essential for host type I IFN-mediated antiviral response. MDPI 2022-08-24 /pmc/articles/PMC9502845/ /pubmed/36146669 http://dx.doi.org/10.3390/v14091862 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Chen
He, Wen-Feng
Li, Long-Xi
Chen, Jing
Yang, Guo-Qing
Chang, Hong-Tao
Liu, Hui-Min
Interferon-Stimulated Gene 15 Knockout in Mice Impairs IFNα-Mediated Antiviral Activity
title Interferon-Stimulated Gene 15 Knockout in Mice Impairs IFNα-Mediated Antiviral Activity
title_full Interferon-Stimulated Gene 15 Knockout in Mice Impairs IFNα-Mediated Antiviral Activity
title_fullStr Interferon-Stimulated Gene 15 Knockout in Mice Impairs IFNα-Mediated Antiviral Activity
title_full_unstemmed Interferon-Stimulated Gene 15 Knockout in Mice Impairs IFNα-Mediated Antiviral Activity
title_short Interferon-Stimulated Gene 15 Knockout in Mice Impairs IFNα-Mediated Antiviral Activity
title_sort interferon-stimulated gene 15 knockout in mice impairs ifnα-mediated antiviral activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502845/
https://www.ncbi.nlm.nih.gov/pubmed/36146669
http://dx.doi.org/10.3390/v14091862
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