Innate immune control of influenza virus interspecies adaptation via IFITM3
Abstract Influenza virus pandemics are caused by viruses from animal reservoirs that adapt to efficiently infect and replicate in human hosts. Here, we investigate whether Interferon-Induced Transmembrane Protein 3 (IFITM3), a host antiviral factor with known human deficiencies, plays a role in inte...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53792-3 |
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| _version_ | 1846121803156553728 |
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| author | Parker J. Denz Samuel Speaks Adam D. Kenney Adrian C. Eddy Jonathan L. Papa Jack Roettger Sydney C. Scace Adam Rubrum Emily A. Hemann Adriana Forero Richard J. Webby Andrew S. Bowman Jacob S. Yount |
| author_facet | Parker J. Denz Samuel Speaks Adam D. Kenney Adrian C. Eddy Jonathan L. Papa Jack Roettger Sydney C. Scace Adam Rubrum Emily A. Hemann Adriana Forero Richard J. Webby Andrew S. Bowman Jacob S. Yount |
| author_sort | Parker J. Denz |
| collection | DOAJ |
| description | Abstract Influenza virus pandemics are caused by viruses from animal reservoirs that adapt to efficiently infect and replicate in human hosts. Here, we investigate whether Interferon-Induced Transmembrane Protein 3 (IFITM3), a host antiviral factor with known human deficiencies, plays a role in interspecies virus infection and adaptation. We find that IFITM3-deficient mice and human cells can be infected with low doses of avian influenza viruses that fail to infect WT counterparts, identifying a new role for IFITM3 in controlling the minimum infectious virus dose threshold. Remarkably, influenza viruses passaged through Ifitm3 −/− mice exhibit enhanced host adaptation, a result that is distinct from viruses passaged in mice deficient for interferon signaling, which exhibit attenuation. Our data demonstrate that IFITM3 deficiency uniquely facilitates potentially zoonotic influenza virus infections and subsequent adaptation, implicating IFITM3 deficiencies in the human population as a vulnerability for emergence of new pandemic viruses. |
| format | Article |
| id | doaj-art-8acccb6fc2d840fe97cb64b953889aa7 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8acccb6fc2d840fe97cb64b953889aa72024-12-15T12:10:00ZengNature PortfolioNature Communications2041-17232024-10-0115111110.1038/s41467-024-53792-3Innate immune control of influenza virus interspecies adaptation via IFITM3Parker J. Denz0Samuel Speaks1Adam D. Kenney2Adrian C. Eddy3Jonathan L. Papa4Jack Roettger5Sydney C. Scace6Adam Rubrum7Emily A. Hemann8Adriana Forero9Richard J. Webby10Andrew S. Bowman11Jacob S. Yount12Department of Microbial Infection and Immunity, The Ohio State University College of MedicineDepartment of Microbial Infection and Immunity, The Ohio State University College of MedicineDepartment of Microbial Infection and Immunity, The Ohio State University College of MedicineDepartment of Microbial Infection and Immunity, The Ohio State University College of MedicineDepartment of Microbial Infection and Immunity, The Ohio State University College of MedicineDepartment of Microbial Infection and Immunity, The Ohio State University College of MedicineDepartment of Microbial Infection and Immunity, The Ohio State University College of MedicineDepartment of Infectious Diseases, St. Jude Children’s Research HospitalDepartment of Microbial Infection and Immunity, The Ohio State University College of MedicineDepartment of Microbial Infection and Immunity, The Ohio State University College of MedicineDepartment of Infectious Diseases, St. Jude Children’s Research HospitalViruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State UniversityDepartment of Microbial Infection and Immunity, The Ohio State University College of MedicineAbstract Influenza virus pandemics are caused by viruses from animal reservoirs that adapt to efficiently infect and replicate in human hosts. Here, we investigate whether Interferon-Induced Transmembrane Protein 3 (IFITM3), a host antiviral factor with known human deficiencies, plays a role in interspecies virus infection and adaptation. We find that IFITM3-deficient mice and human cells can be infected with low doses of avian influenza viruses that fail to infect WT counterparts, identifying a new role for IFITM3 in controlling the minimum infectious virus dose threshold. Remarkably, influenza viruses passaged through Ifitm3 −/− mice exhibit enhanced host adaptation, a result that is distinct from viruses passaged in mice deficient for interferon signaling, which exhibit attenuation. Our data demonstrate that IFITM3 deficiency uniquely facilitates potentially zoonotic influenza virus infections and subsequent adaptation, implicating IFITM3 deficiencies in the human population as a vulnerability for emergence of new pandemic viruses.https://doi.org/10.1038/s41467-024-53792-3 |
| spellingShingle | Parker J. Denz Samuel Speaks Adam D. Kenney Adrian C. Eddy Jonathan L. Papa Jack Roettger Sydney C. Scace Adam Rubrum Emily A. Hemann Adriana Forero Richard J. Webby Andrew S. Bowman Jacob S. Yount Innate immune control of influenza virus interspecies adaptation via IFITM3 Nature Communications |
| title | Innate immune control of influenza virus interspecies adaptation via IFITM3 |
| title_full | Innate immune control of influenza virus interspecies adaptation via IFITM3 |
| title_fullStr | Innate immune control of influenza virus interspecies adaptation via IFITM3 |
| title_full_unstemmed | Innate immune control of influenza virus interspecies adaptation via IFITM3 |
| title_short | Innate immune control of influenza virus interspecies adaptation via IFITM3 |
| title_sort | innate immune control of influenza virus interspecies adaptation via ifitm3 |
| url | https://doi.org/10.1038/s41467-024-53792-3 |
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