Defining host factors of susceptibility and resistance to african swine fever in domestic and wild suids

Project summary

African swine fever (ASF) is a major animal health and welfare threat to pigs: in the 2018-2019 period, it was responsible for the loss of an estimated 300 million pigs from production in China, representing over one billion USD of lost revenue. While domestic pigs and wild boars are highly sensitive to infection, wild African suids are resistant to the disease despite some level of viral replication. ASFV pathogenicity in these species remains largely unexplored, in part due to the lack of cellular tools necessary to perform a comparative analysis of the innate host responses to ASFV in different species.

We hypothesize that susceptibility and resilience to ASFV is determined by intrinsic features of macrophages, like the innate immune response and the activity of Interferon Stimulated Genes (ISGs). To understand the basis of resistance to ASFV in these different species, we have generated an Induced Pluripotent Stem cell-based platform for the in vitro generation of macrophages (PSCdMs) from both domestic and wild African suids. The ASF-RESIST project will leverage this unique resource to compare the innate immune response of wild and domestic suids to ASFV.

Using transcriptomic, interactomic and imaging approaches, we will characterize these different models and identify host factors differentially expressed after infection in domestic/wild suids. Comparative bioinformatic analyses will identify key differences between domestic and wild suids underpinning resistance/susceptibility. Systematic screening of the antiviral activity of ISGs will identify key ASFV restriction factors and determine their contribution to host susceptibility. The ASF-RESIST project will provide a mechanistic explanation to the resistance of certain species to clinical infection. Identifying novel antiviral pathways will help to improve the resilience of pig herds against ASFV outbreaks through improved breeding programs or precision editing.