Emergence of a Novel Highly Pathogenic Recombinant RNA Virus of Picornaviridae with Blood–Brain Barrier Breaching Capability in China

Picornaviruses pose a significant threat to both human and animal health, causing many diseases in humans and swine. Porcine sapelovirus (PSV) is a globally reported enteric picornavirus commonly associated with subclinical or mild enteric infections in swine populations. Critically, unlike other neurotropic picornaviruses such as Enterovirus A71, no PSV strain has been reported to breach the blood–brain barrier (BBB). Since 2023, outbreaks of diarrhea with concurrent neurological signs like ataxia and lameness have been observed in weaned piglets across China, in particular, on a farm in Zhejiang province in 2025 with 100% morbidity and 20% mortality among the cases. Routine diagnostics ruled out common swine pathogens, but qPCR was positive for PSV. We successfully isolated three PSV strains (ZJ, FJ, SD) from affected piglets. Genetic analysis revealed that the PSV-ZJ is a novel recombinant between strains YC2011/2012 (China, 2011) and XTND/2019 (Vietnam, 2018). Pathogenicity assessment confirmed that the recombinant PSV-ZJ is highly pathogenic, causing severe diarrhea, growth retardation, and significant viral shedding via the respiratory and digestive tracts. qPCR and histopathology confirmed viral presence in intestinal and brain tissues, indicating that PSV-ZJ can cross the blood–brain barrier. This study presents the first quantitative viral load and histopathological data for a highly pathogenic recombinant PSV strain in China and emphasizes the critical role of recombination in driving viral virulence evolution, necessitating enhanced surveillance and the development of targeted preventive strategies.