Characterization of disease tolerance and antiviral pathways in mammalian reservoir species toward emerging respiratory viruses with pandemic poteial

• Applicant: Dr. Sophie-Marie Aicher
• Subject Area: Virology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 559180272

The term zoonosis describes transmission of a pathogen from an animal species to humans. Zoonotic viruses of public health concern (e.g. Ebola virus or Severe Acute Respiratory Syndrome Coronavirus 2) have increasingly caused large-scale international outbreaks or global pandemics. The complex relationship between viruses, their hosts, and the ecosystems they share, raises major challenges for risk evaluation and mitigation. To address this gap, One Health approaches aiming to better understand the human-animal-environment interface and involving multidisciplinary efforts to promote health for all are being implemented. Zoonotic viruses are non- or minimally pathogenic in their reservoir animal hosts while infection outcomes in humans can range from severe disease to death. To date, however, little is known about the immune features that promote viral tolerance in reservoir hosts, such as wildlife or domestic mammals. This project will therefore focus on the animal-human interface of zoonotic viruses with pandemic potential, focusing SARS-CoV-2 and highly pathogenic avian influenza (HPAI) viruses. I aim to (i) establish novel cellular model systems for mammalian hosts of emerging viral infections, (ii) compare the innate immune landscape upon infection between symptomatic and asymptomatic host species, and (iii) determine the molecular effectors and antiviral pathways facilitating tolerance towards viral infection in relevant reservoir species while applying a multidisciplinary approach. I will characterize a divergent SARS-CoV-2 strain isolated from Canadian white-tailed deer (WTD), a newly established wildlife reservoir of SARS-CoV-2 in North America, and decipher their antiviral immune responses upon infection using an transcriptomic approach. Using the same methodology, I will compare and contrast innate immune mechanisms of pigs as asymptomatic mammalian host of newly emerging HPAI viruses with ferrets which display severe signs of infection and high mortality rates. In addition to better understanding the host barriers to infection and thus evaluating the risks posed these ecologically critical species, this project will greatly support the development of tools for non-model animals. These protocols can be extrapolated for other neglected animal reservoirs and thus lead to a major step towards future pandemic preparedness.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Dr. Samira Mubareka