Barriers to influenza viruses cross-species transmission

 

Supervisor: Professor Massimo Palmarini, School of Infection & Immunity 

 

Rotation project:

Influenza A viruses (IAV) are the cause of major global health burden and circulate both in humans and animal species including domestic poultry, pigs and horses. Wild aquatic birds are the main natural reservoir of IAV and are a source of infection for domestic gallinaceous species, and other species. Avian IAV can also exchange genomic segments (reassort) with viruses established in susceptible species. In humans, all the four influenza pandemics were caused by viruses containing at least some genomic segments of avian origin. Importantly, spillover of avian IAV into humans may result in severe or even lethal disease. For example, avian viruses such as H7N9 and H5N1 have caused more than 600 human deaths in different epizootic clusters. These spillover events are typically not followed by extensive human-to-human transmission chains, but they are a risk to global health as they could enable the first step towards human adaptation and the generation of pandemic IAV strains. 

Multiple barriers have been identified that hamper avian IAV transmission and adaptation in humans including an interferon stimulated gene, BTN3A3, that we recently identified[1]. However, several gaps remain in our understanding of how certain avian IAV subtypes/lineages are able to cross the species-barrier and spill over in humans or other mammals. The aims of the rotation project are to investigate how orthologous restriction factors from a variety of animal species, including those susceptible or resistant to avian IAV, blocks virus replication. We will use both viruses that have been able to spillover in humans,  such as H7N9 and H5N1, and avian viruses that have not crossed the species barrier despite circulating extensively in birds. Understanding what makes emerging viruses succeed or fail to spillover, and possibly thrive, in human populations are crucial to understand how we manage viral emergence.

 

References

 

  1. Pinto RM, Bakshi S, Lytras S, Zakaria MK, Swingler S, Worrell JC, et al. BTN3A3 evasion promotes the zoonotic potential of influenza A viruses. Nature. 2023. Epub 2023/06/29. doi: 10.1038/s41586-023-06261-8. PubMed PMID: 37380775.