C57BL/6J and C57BL/6NJ Mice Are Differentially Susceptible to Inflammation-Associated Disease Caused by Influenza A Virus
Influenza viruses cause seasonal epidemics and sporadic pandemics, and are a major burden on human health. To develop better countermeasures and improve influenza disease outcomes, a clearer understanding of influenza pathogenesis is necessary. Host genetic factors have emerged as potential regulato...
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| Format: | Article |
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Frontiers Media S.A.
2019-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.03307/full |
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| author | Amie J. Eisfeld David J. Gasper M. Suresh Yoshihiro Kawaoka Yoshihiro Kawaoka Yoshihiro Kawaoka |
| author_facet | Amie J. Eisfeld David J. Gasper M. Suresh Yoshihiro Kawaoka Yoshihiro Kawaoka Yoshihiro Kawaoka |
| author_sort | Amie J. Eisfeld |
| collection | DOAJ |
| description | Influenza viruses cause seasonal epidemics and sporadic pandemics, and are a major burden on human health. To develop better countermeasures and improve influenza disease outcomes, a clearer understanding of influenza pathogenesis is necessary. Host genetic factors have emerged as potential regulators of human influenza disease susceptibility, and in the mouse model, genetic background has been clearly linked to influenza pathogenicity. Here, we show that C57BL/6J mice are significantly more susceptible to disease caused by a 2009 pandemic H1N1 virus, an H7N9 virus, and a highly pathogenic H5N1 influenza virus compared to the closely related substrain, C57BL/6NJ. Mechanistically, influenza virus infection in C57BL/6J mice results in earlier presentation of edema, increased immune cell infiltration, higher levels of inflammatory cytokines, greater tissue damage, and delayed activation of regenerative processes in infected lung tissues compared to C57BL/6NJ mice. These differences are not dependent on virus replication levels. Six genes with known coding region differences between C57BL/6J and C57BL/6NJ strains exhibit increased transcript levels in influenza virus-infected mouse lungs, suggesting potential contributions to regulation of disease susceptibility. This work uncovers a previously unappreciated difference in disease susceptibility between the closely related C57BL/6J and C57BL/6NJ mice, which may be exploited in future studies to identify host factors and/or specific genetic elements that regulate host-dependent inflammatory mechanisms involved in influenza virus pathogenicity. |
| first_indexed | 2024-12-13T01:21:37Z |
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| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-13T01:21:37Z |
| publishDate | 2019-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-f718b528b58d47cf836ef37786c7326c2022-12-22T00:04:13ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-01-01910.3389/fmicb.2018.03307427388C57BL/6J and C57BL/6NJ Mice Are Differentially Susceptible to Inflammation-Associated Disease Caused by Influenza A VirusAmie J. Eisfeld0David J. Gasper1M. Suresh2Yoshihiro Kawaoka3Yoshihiro Kawaoka4Yoshihiro Kawaoka5Department of Pathobiological Sciences, University of Wisconsin–Madison, Madison, WI, United StatesDepartment of Pathobiological Sciences, University of Wisconsin–Madison, Madison, WI, United StatesDepartment of Pathobiological Sciences, University of Wisconsin–Madison, Madison, WI, United StatesDepartment of Pathobiological Sciences, University of Wisconsin–Madison, Madison, WI, United StatesDivision of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanInternational Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanInfluenza viruses cause seasonal epidemics and sporadic pandemics, and are a major burden on human health. To develop better countermeasures and improve influenza disease outcomes, a clearer understanding of influenza pathogenesis is necessary. Host genetic factors have emerged as potential regulators of human influenza disease susceptibility, and in the mouse model, genetic background has been clearly linked to influenza pathogenicity. Here, we show that C57BL/6J mice are significantly more susceptible to disease caused by a 2009 pandemic H1N1 virus, an H7N9 virus, and a highly pathogenic H5N1 influenza virus compared to the closely related substrain, C57BL/6NJ. Mechanistically, influenza virus infection in C57BL/6J mice results in earlier presentation of edema, increased immune cell infiltration, higher levels of inflammatory cytokines, greater tissue damage, and delayed activation of regenerative processes in infected lung tissues compared to C57BL/6NJ mice. These differences are not dependent on virus replication levels. Six genes with known coding region differences between C57BL/6J and C57BL/6NJ strains exhibit increased transcript levels in influenza virus-infected mouse lungs, suggesting potential contributions to regulation of disease susceptibility. This work uncovers a previously unappreciated difference in disease susceptibility between the closely related C57BL/6J and C57BL/6NJ mice, which may be exploited in future studies to identify host factors and/or specific genetic elements that regulate host-dependent inflammatory mechanisms involved in influenza virus pathogenicity.https://www.frontiersin.org/article/10.3389/fmicb.2018.03307/fullinfluenzapathogenicityH1N1H5N1H7N9inflammation |
| spellingShingle | Amie J. Eisfeld David J. Gasper M. Suresh Yoshihiro Kawaoka Yoshihiro Kawaoka Yoshihiro Kawaoka C57BL/6J and C57BL/6NJ Mice Are Differentially Susceptible to Inflammation-Associated Disease Caused by Influenza A Virus Frontiers in Microbiology influenza pathogenicity H1N1 H5N1 H7N9 inflammation |
| title | C57BL/6J and C57BL/6NJ Mice Are Differentially Susceptible to Inflammation-Associated Disease Caused by Influenza A Virus |
| title_full | C57BL/6J and C57BL/6NJ Mice Are Differentially Susceptible to Inflammation-Associated Disease Caused by Influenza A Virus |
| title_fullStr | C57BL/6J and C57BL/6NJ Mice Are Differentially Susceptible to Inflammation-Associated Disease Caused by Influenza A Virus |
| title_full_unstemmed | C57BL/6J and C57BL/6NJ Mice Are Differentially Susceptible to Inflammation-Associated Disease Caused by Influenza A Virus |
| title_short | C57BL/6J and C57BL/6NJ Mice Are Differentially Susceptible to Inflammation-Associated Disease Caused by Influenza A Virus |
| title_sort | c57bl 6j and c57bl 6nj mice are differentially susceptible to inflammation associated disease caused by influenza a virus |
| topic | influenza pathogenicity H1N1 H5N1 H7N9 inflammation |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.03307/full |
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