Comparative genomic analysis of pigs differing in survival following African swine fever virus infection

Abstract

African swine fever remains a major constraint on global pig production because effective treatment is unavailable, and disease control relies primarily on biosecurity and outbreak management. Field observations from endemic regions increasingly suggest that some domestic pigs can survive exposure to ASFV. Therefore, the aim of this study was to characterize genomic differences between Mozambican Landim pigs that survived or died after natural ASFV infection and to identify variants potentially associated with differential disease survival. Whole-genome sequencing was performed on 32 naturally exposed Landim pigs, including 16 survivors and 16 non-survivors, and the resulting reads were aligned to the Sscrofa11.1 reference genome. Variant frequencies were compared between groups, and functional annotation was performed. Genetic structure was assessed using PCA, genetic distance-based clustering, and admixture. The data revealed marked genomic differentiation between survivors and non-survivors. Comparative analysis identified 4,804 polymorphisms that significantly differentiated, of which 45.0% were intergenic. Missense variants were identified in the TTC12 and WWC1 genes, and functional annotation of genes harboring significantly differentiating variants indicated processes related to immune regulation, T-cell activation, intracellular signaling, cytoskeletal organization, vesicular transport, ubiquitin-dependent proteostasis, and lipid metabolism. Given the marked genetic stratification between survivor and non-survivor groups, the observed differences between them cannot be unambiguously separated from underlying population structure. Therefore, although some of the identified variants may contribute to differential survival following ASFV exposure, the findings should be considered exploratory and require validation in larger, independent, genetically comparable populations.