22-ICRAD Call 2 Emerging porcine influenza and coronaviruses (EPICVIR)

Influenza and coronaviruses have caused some of the deadliest pandemics in humans, and swine are key viral reservoirs. Influenza viruses of type A and porcine respiratory coronavirus are enzootic in swine, but they differ in pathogenicity and immune control. Cattle are the natural host of influenza D virus, but it is now an emerging virus in swine, and its pathogenesis remains underexplored. Swine Influenza viruses of type A have enormous and still increasing genetic diversity with many "reassortant" (i.e. when genetic exchange occurs during co-infection involving different viruses or viral strains) genotypes circulating simultaneously, and is a proven zoonotic and pandemic threat. The pandemic potential of porcine respiratory coronavirus and swine Influenza D is uncertain.

In this project, we aim to answer questions about the transmissibility and pathogenicity of these viruses. We aim to better understand what the transmission dynamics of these viruses are between swine and from swine to ferrets (which can be used as a model for humans). We also aim to study the immune response against these viruses, and what are the main factors that tip the balance to mild or severe disease. One of the main aims is to determine the zoonotic potential (i.e. the potential for these viruses to jump from a non-human animal to humans) of these viruses, and which ones in particular pose a higher risk. To do this, we aim to integrate data arising from different experiments by using relevant mathematical, computational and statistical techniques.

Our results will help predict the zoonotic potential, transmission, and pathogenicity of existing and emerging swine Influenza viruses and porcine respiratory coronaviruses.

Influenza and coronaviruses have caused some of the deadliest pandemics in humans, and swine are key viral reservoirs. Influenza viruses of type A (swIAV) and porcine respiratory coronavirus (PRCV) are enzootic in swine and target epithelial cells of the airways. Still, they differ in pathogenicity and immune control. Cattle are the natural host of influenza D virus, but it is now an emerging virus in swine (swIDV), and its pathogenesis remains underexplored. SwIAV has enormous and still increasing genetic diversity with many "reassortant" genotypes circulating simultaneously, and is a proven zoonotic and pandemic threat. The pandemic potential of PRCV and swIDV is uncertain.

We shall compare the transmission, pathogenesis and host tropism of 6 different swIAV genotypes, swIDV and PRCV, to address 4 questions: 1) What are the transmission dynamics of swIVs and PRCV between swine and from swine to ferrets, which are used as a model for humans. 2) What key early events and immune mediators govern the outcome of swIV and PRCV exposure and may tip the balance to mild or severe disease? 3) What is the zoonotic potential of swIV and PRCV? Do some of the novel H1 swIAV genotypes pose a higher risk than the well-known swIAV? How efficiently do swIDV and PRCV replicate in human airways? Which viral traits may contribute to host switching? 4) Can an integrated mathematical model of viral replication, transmission, pathogenesis and immune control identify key events in the virus-host interaction to inform control strategies?

We will perform in vivo studies (Q1-2) in the swine and ferret host, and in vitro studies (Q3) in differentiated airway cultures of swine, humans, and ferrets, with maximal similarity to the in vivo situation. Finally, we will use novel mathematical models to provide quantitative information from the integrated data (Q4).

Our results will help predict the zoonotic potential, transmission, and pathogenicity of existing and emerging swIVs and PRCVs