Divergent porcine astrovirus 4: distinct respiratory and gastrointestinal clades with genetic differences

In 2016, porcine astrovirus 4 (PoAstV4), historically associated with gastrointestinal infections, was first reported in piglets with acute respiratory disease in Oklahoma. Cases of PoAstV4 with consistent respiratory epitheliotropic viral lesions were later confirmed in 2023. Analyses of 38 new whole genomes indicate that respiratory-associated PoAstV4 strains are genetically distinct from those found associated with gastrointestinal disease, with a divergence of approximately 22.5–26%. A total of 36 distinct nucleotide mutations, differing between the two clades, were identified: 17 in ORF1ab and 19 in ORF2. A consistent pattern of 11–12 amino acid differences in the C-acidic region was observed. Bayesian phylogenetic methods suggested that the most recent common ancestor for the respiratory clade was identified in 2003 (90% HPD: 1994.5–2010). Further experimental validation is needed to determine whether the identified genetic differences affect respiratory tropism. However, this study provides a foundation for investigating potential tissue-specific adaptations and may enhance diagnostic accuracy.