Phd Project: Identification of Escape H9 and H5 Influenza Mutants Due to Vaccination

**Objectives of the PhD project**

Highly pathogenic avian influenza (HPAI) is a transboundary disease with zoonotic potential that poses significant threats to animal health, human health, and the global economy. Since 2020, the world has experienced unprecedented HPAI H5N1 epidemics of a particular lineage belonging to clade 2.3.4.4b. This epidemic has been associated with a wide geographical spread (5 continents), an increase in number of mammal infections and early 2024 cases in dairy cows in the US, with already 70 associated human infections in the USA as of April 2025. This highlights the concerning possibility that the virus has successfully crossed the species barrier and transmits efficiently. While HPAIV H5N1 has not caused cattle infections outside the USA so far, a recent study has shown that the American genotype (B3.13) infecting American cattle is not the only clade 2.3.4.4b strain able to efficiently infect dairy cow utter. In parallel, a recent infection of sheep in the UK was reported with a European genotype (DI) of HPAIV H5N1, and a serology study highlighted that cattle is exposed to swine and Human influenza A viruses.

In the present PhD project, we will thus tackle the question of ruminants susceptibility to avian and seasonal influenza viruses infection using in vitro and ex vivo approaches and looking in respiratory and mammary gland cells and tissues. Both HPAIV H5N1 (European and American lineage viruses) and low pathogenic avian influenza viruses will be tested. Molecular determinants of viral tropism will also be studied and a relevant strain will be selected for full phenotypic characterization _in vivo_.

**Supervisor**

**Key references**

1. European Food Safety Authority, European Centre for Disease Prevention and Control, European Union Reference Laboratory for Avian Influenza, Alexakis L., Buczkowski H.,, Fusaro A., Gonzales J.L., Kuiken T., Ståhl K., Staubach C., Svartström O., Terregino C., Willgert K., Melo M., Kohnle L., Avian influenza overview December 2024-March 2025. _**EFSA Journal**_. **2025**, doi: 10.2903/j.efsa.2025.9352.

2. Sanogo I.N., Guinat C., Dellicour S., Diakité M.A., Niang M., Koita O.A., Camus C.,, Genetic insights of H9N2 avian influenza viruses circulating in Mali and phylogeographic patterns in Northern and Western Africa. _**Virus Evolution**_. **2024**, 10(1):veae011. doi: 10.1093/ve/veae011.

3. Gaudino M., Lion A., Sagné E., Nagamine B., Oliva J., Terrier O., Errazuriz-Cerda E., Scribe A., Sikht F.Z., Simon E., Foret-Lucas C., Gausserès B., Lion J., Moreno A., Dordet-Frisoni E., Baranowski E., Volmer R.,, Meyer G.*, The activation of the RIG-I/MDA5 signalling pathway upon Influenza D virus infection impairs the pulmonary pro-inflammatory response triggered by Mycoplasma bovis superinfection. _**Journal of Virology**_**. 2023;**e0142322. doi: 10.1128/jvi.01423-22.

4. Xie R., Edwards K.M., Wille M., Wei X., Wong S.S., Zanin M., El-Shesheny R., Ducatez M., Poon L.L.M., Kayali G., Webby R.J., Dhanasekaran V., The episodic resurgence of highly pathogenic avian influenza H5 virus. Nature. 2023, 622(7984): 810-817. doi: 10.1038/s41586-023-06631-2.

5. Gaudino M., Chiapponi C., Moreno A., Zohari S., O'Donovan T., Ryan E., Quineless E., Sausy A., Oliva J., Salem E., Fusade-Boyer M., Meyer G., Hübschen J., Saegerman C., *, Snoeck C.J.*, Evolutionary and temporal dynamics of emerging Influenza D virus in Europe (2009-2022). _**Virus Evolution.**_**2022;**8(2):veac081. doi: 10.1093/ve/veac081.

6. Sanogo I.N., Djegui F., Akpo Y., Gnanvi C., Dupré G., Rubrum A., Jeevan T., McKenzie P., Webby R.J.,, Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus in Poultry, Benin, 2021. _**Emerging Infectious Diseases**_. **2022**; 8(12):2534-2537. doi: 10.3201/eid2812.221020.

7. Fusade-Boyer M., Djegui F., Batawui K., Byuragaba D.K., Jones J.C., Wabwire-Mangeni F., Erima B., Atim G., Ukuli Q.A., Tugume T., Dogno K., Adjabli K., Nzuzi M., Adjin R., Jeevan T., Rubrum A., Go-Maro W., Kayali G., McKenzie P., Webby R.J.,, Antigenic and molecular characterization of low pathogenic avian influenza A(H9N2) viruses in sub-Saharan Africa from 2017 through 2019. _**Emerging Microbes and Infections**_. 10(1):753-761. **2021.**doi: 10.1080/22221751.2021.1908097.

8. Lion A., Secula A., Rançon C., Boulesteix O., Pinard A., Deslis A., Hägglund S., Salem E., Cassard H., Näslund K., Gaudino M., Moreno A., Brocchi E., Delverdier M., Zohari S., Baranowski E., Valarcher J.F.,, Meyer G., Enhanced Pathogenesis Caused by Influenza D Virus and Mycoplasma bovis Coinfection in Calves: a Disease Severity Linked with Overexpression of IFN-γ as a Key Player of the Enhanced Innate Immune Response in Lungs, _**Microbiology Spectrum.**_ **2021**; 9(3):e0169021. doi: 10.1128/spectrum.01690-21.

**Research location**

**Training and skills**

**INRAE presentation**

The French National Research Institute for Agriculture, Food, and Environment (INRAE) is a major player in research and