دورية أكاديمية
Dissemination of influenza B virus to the lower respiratory tract of mice is restricted by the interferon response.
| العنوان: | Dissemination of influenza B virus to the lower respiratory tract of mice is restricted by the interferon response. |
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| المؤلفون: | Schwab LSU; Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia., Do THT; Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia., Pilapitiya D; Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia., Koutsakos M; Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia. |
| المصدر: | Journal of virology [J Virol] 2024 Jun 13; Vol. 98 (6), pp. e0160423. Date of Electronic Publication: 2024 May 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Society For Microbiology Original Publication: Baltimore, American Society for Microbiology. |
| مواضيع طبية MeSH: | Influenza B virus*/physiology , Influenza B virus*/immunology , Orthomyxoviridae Infections*/immunology , Orthomyxoviridae Infections*/virology , Lung*/virology , Lung*/immunology , Virus Replication*, Animals ; Mice ; Disease Models, Animal ; Interferons/metabolism ; Interferons/immunology ; Myxovirus Resistance Proteins/metabolism ; Myxovirus Resistance Proteins/genetics ; Receptor, Interferon alpha-beta/genetics ; Receptor, Interferon alpha-beta/deficiency ; Mice, Inbred C57BL ; Host-Pathogen Interactions/immunology ; Respiratory Tract Infections/virology ; Respiratory Tract Infections/immunology ; Female ; Interferon-gamma/metabolism ; Trachea/virology |
| مستخلص: | The global burden of disease caused by influenza B virus (IBV) is substantial; however, IBVs remain overlooked. Understanding host-pathogen interactions and establishing physiologically relevant models of infection are important for the development and assessment of therapeutics and vaccines against IBV. In this study, we assessed an upper respiratory tract (URT)-restricted model of mouse IBV infection, comparing it to the conventional administration of the virus to the total respiratory tract (TRT). We found that URT infections caused by different strains of IBV disseminate to the trachea but resulted in limited dissemination of IBV to the lungs. Infection of the URT did not result in weight loss or systemic inflammation even at high inoculum doses and despite robust viral replication in the nose. Dissemination of IBV to the lungs was enhanced in mice lacking functional type I IFN receptor (IFNAR2), but not IFNγ. Conversely, in mice expressing the IFN-inducible gene Mx1, we found reduced IBV replication in the lungs and reduced dissemination of IBV from the URT to the lungs. Inoculation of IBV in both the URT and TRT resulted in seroconversion against IBV. However, priming at the TRT conferred superior protection from a heterologous lethal IBV challenge compared to URT priming, as determined by improved survival rates and reduced viral replication throughout the respiratory tract. Overall, our study establishes a URT-restricted IBV infection model, highlights the critical role of IFNs in limiting dissemination of IBV to the lungs, and also demonstrates that the lack of viral replication in the lungs may impact protection from subsequent infections. Importance: Our study investigated how influenza B virus (IBV) spreads from the nose to the lungs of mice and the impact this has on disease and protection from re-infection. We found that when applied to the nose only, IBV does not spread very efficiently to the lungs in a process controlled by the interferon response. Priming immunity at the nose only resulted in less protection from re-infection than priming immunity at both the nose and lungs. These insights can guide the development of potential therapies targeting the interferon response as well as of intranasal vaccines against IBV. Competing Interests: M.K. has acted as a consultant for the Sanofi group of companies. The other authors declare no competing interests. |
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| معلومات مُعتمدة: | Morningside Foundation (); DHAC | National Health and Medical Research Council (NHMRC) |
| فهرسة مساهمة: | Keywords: Mx; influenza; innate immunity; interferon; upper respiratory tract |
| المشرفين على المادة: | 9008-11-1 (Interferons) 0 (Myxovirus Resistance Proteins) 156986-95-7 (Receptor, Interferon alpha-beta) 82115-62-6 (Interferon-gamma) 0 (Mx1 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240523 Date Completed: 20240613 Latest Revision: 20240714 |
| رمز التحديث: | 20240714 |
| مُعرف محوري في PubMed: | PMC11237704 |
| DOI: | 10.1128/jvi.01604-23 |
| PMID: | 38780249 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5514 |
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| DOI: | 10.1128/jvi.01604-23 |