Funding entity Ministerio de Ciencia e Innovación (MCI)/Agencia Estatal de Investigación (AEI)
Participated by Ghent University, Faculty of Veterinary Medicine, Utrecht University Department of Biomolecular Health Sciences, Centro de Investigaciones Biológicas Margarita Salas Molecular Biomedicine, Pirbright Institute Host responses, University of Leeds Applied Mathematics
Influenza viruses and coronaviruses have caused some of the deadliest pandemics in humans, and pigs are natural reservoirs. Swine influenza A viruses (swIAV) and porcine respiratory coronavirus (PRCV) are enzootic in pigs, infecting airway epithelial cells. However, they differ in their pathogenicity and immune response. Cattle are the natural host for influenza D virus (IDV), but it is now an emerging virus in swine (swIDV), and its pathogenesis is unknown. The genetic diversity of the swine influenza virus is enormous and continues to increase, with many "reassortant" genotypes co-circulating and constituting a zoonotic threat with proven pandemic characteristics. The pandemic potential of PRCV and swIDV is not known.
We compare the transmission, pathogenesis, and host tropism of six different genotypes of swIAV, swIDV, and PRCV to answer the following four questions:
1) What are the transmission dynamics of swIVs and PRCV between pigs and from pigs to ferrets? The latter is a model for humans.
2) What key early events and immune mediators govern the outcome of swIV and PRCV exposure that may tip the balance toward mild or severe disease?
3) What is the zoonotic potential of swIV and PRCV? Do some new H1 swIAV genotypes pose a higher risk than those already known? How efficiently do swIDV and PRCV replicate in the human airways?
What viral traits can contribute to host switching?
4) Can an integrated mathematical model of viral replication, transmission, pathogenesis, and immune control identify key events in virus-host interaction to inform control strategies?
We perform in vivo studies (Q1, 2) in the porcine and ferret host and in vitro studies (Q3) in discrete cultures of the porcine, human, and ferret airways, with maximum similarity to the in vivo situation. Finally, we use novel mathematical models to provide quantitative information from the integrated data (Q4).
Our results help predict the zoonotic potential, transmission, and pathogenicity of existing and emerging swIVs and PRCVs.
Layman's summary: Influenza viruses and coronaviruses have caused severe human pandemics, and pigs are natural reservoirs. By comparing in-vitro studies, animals, and mathematical models, we help predict the zoonotic potential and pathogenicity of existing and emerging viruses.
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