Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivo
The rapid spread of infectious diseases presents a significant global threat, with seasonal influenza viruses, leading to 290,000–650,000 deaths annually. Emerging high pathogenic influenza strains from animals such as H5N1 and H7N9 further exacerbates pandemic risks. While developing effective vacc...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1608074/full |
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| author | Tiong Kit Tan Tiong Kit Tan Pramila Rijal Pramila Rijal Kuan-Ying A. Huang Stephen C. Hyde Deborah R. Gill Alain R. Townsend Alain R. Townsend |
| author_facet | Tiong Kit Tan Tiong Kit Tan Pramila Rijal Pramila Rijal Kuan-Ying A. Huang Stephen C. Hyde Deborah R. Gill Alain R. Townsend Alain R. Townsend |
| author_sort | Tiong Kit Tan |
| collection | DOAJ |
| description | The rapid spread of infectious diseases presents a significant global threat, with seasonal influenza viruses, leading to 290,000–650,000 deaths annually. Emerging high pathogenic influenza strains from animals such as H5N1 and H7N9 further exacerbates pandemic risks. While developing effective vaccines and therapeutics is critical, the evaluation of these interventions is constrained by the requirement for high biosafety containment facilities. To circumvent these challenges, we developed S-Lux, a replication-deficient, single-cycle recombinant influenza virus expressing firefly luciferase (Flux) as a reporter protein. S-Lux can be pseudotyped with haemagglutinin from avian influenza, H5 and H7, enabling real-time monitoring of viral infection in vivo, and facilitate therapeutic antibody evaluation in low-containment facilities. In mice, S-Lux infection resulted in dose-dependent bioluminescent expression in the mouse airways and allowed evaluation of neutralising monoclonal antibodies and clearance of infected cells in mice. To extend this system, we generated ES-Lux by pseudotyping with the Ebola Glycoprotein (GP) and demonstrated that ES-Lux can be used to evaluate the efficacy of Ebola GP-targeting antibodies in vivo. Together, S-Lux and ES-Lux enable robust, simple and time-efficient assessment of antiviral therapy targeting influenza and Ebola virus in vivo, overcoming biosafety constraints that limit traditional efficacy studies. |
| format | Article |
| id | doaj-art-7bce2a0b3907417baa12f2573e6e3a82 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-7bce2a0b3907417baa12f2573e6e3a822025-08-20T03:50:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16080741608074Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivoTiong Kit Tan0Tiong Kit Tan1Pramila Rijal2Pramila Rijal3Kuan-Ying A. Huang4Stephen C. Hyde5Deborah R. Gill6Alain R. Townsend7Alain R. Townsend8Medical Research Council (MRC) Translational Immune Discovery Unit, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomChinese Academy of Medical Science-Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomMedical Research Council (MRC) Translational Immune Discovery Unit, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomChinese Academy of Medical Science-Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomGraduate Institute of Immunology and Department of Paediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, TaiwanGene Medicine Research Group, Nuffield Division of Clinical Laboratory Science, Radcliffe Department of Medicine, University of Oxford, Oxford, United KingdomGene Medicine Research Group, Nuffield Division of Clinical Laboratory Science, Radcliffe Department of Medicine, University of Oxford, Oxford, United KingdomMedical Research Council (MRC) Translational Immune Discovery Unit, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomChinese Academy of Medical Science-Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United KingdomThe rapid spread of infectious diseases presents a significant global threat, with seasonal influenza viruses, leading to 290,000–650,000 deaths annually. Emerging high pathogenic influenza strains from animals such as H5N1 and H7N9 further exacerbates pandemic risks. While developing effective vaccines and therapeutics is critical, the evaluation of these interventions is constrained by the requirement for high biosafety containment facilities. To circumvent these challenges, we developed S-Lux, a replication-deficient, single-cycle recombinant influenza virus expressing firefly luciferase (Flux) as a reporter protein. S-Lux can be pseudotyped with haemagglutinin from avian influenza, H5 and H7, enabling real-time monitoring of viral infection in vivo, and facilitate therapeutic antibody evaluation in low-containment facilities. In mice, S-Lux infection resulted in dose-dependent bioluminescent expression in the mouse airways and allowed evaluation of neutralising monoclonal antibodies and clearance of infected cells in mice. To extend this system, we generated ES-Lux by pseudotyping with the Ebola Glycoprotein (GP) and demonstrated that ES-Lux can be used to evaluate the efficacy of Ebola GP-targeting antibodies in vivo. Together, S-Lux and ES-Lux enable robust, simple and time-efficient assessment of antiviral therapy targeting influenza and Ebola virus in vivo, overcoming biosafety constraints that limit traditional efficacy studies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1608074/fullpandemicinfluenzain vivo imagingbioluminescencereporter virus |
| spellingShingle | Tiong Kit Tan Tiong Kit Tan Pramila Rijal Pramila Rijal Kuan-Ying A. Huang Stephen C. Hyde Deborah R. Gill Alain R. Townsend Alain R. Townsend Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivo Frontiers in Immunology pandemic influenza in vivo imaging bioluminescence reporter virus |
| title | Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivo |
| title_full | Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivo |
| title_fullStr | Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivo |
| title_full_unstemmed | Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivo |
| title_short | Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivo |
| title_sort | single cycle pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza ebola and other highly infectious diseases in vivo |
| topic | pandemic influenza in vivo imaging bioluminescence reporter virus |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1608074/full |
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