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Molecular Epidemiology and Pathogenicity Evaluation of Porcine Teschovirus in Tibetan Pigs on the Qinghai-Tibet Plateau of China.

Porcine teschovirus (PTV) is the causative agent of porcine diarrhea and multisystem disorder and poses a global threat to the health of domestic pigs. However, its epidemic and pathogenic characteristics in Tibetan pigs, which are a unique indigenous breed in the Qinghai-Tibet Plateau of China, remain largely unexplored. Here, we conducted a comprehensive investigation during 2024-2025, in which 303 diarrheic fecal samples were collected from 21 farms across eight counties in Ganzi Tibetan Autonomous Prefecture, with an average altitude of 3433 m. RT-PCR testing identified 141 PTV-positive samples, yielding a high positivity rate of 46.5% (141/303). From these positives, 27 VP1 sequences were cloned and sequenced; phylogenetic analysis revealed that 16 strains belonged to Teschovirus A, three strains were divided into Teschovirus B, and three strains formed the interspecies recombinant genotypes (PTV-15/16). Interestingly, five novel strains were classified as undefined genotypes, indicating an extensive genetic diversity among PTV strains circulating in Tibetan pigs. Furthermore, a PTV strain, designated PTV-SCgz-01, was successfully isolated in PK-15 cells, with a near-complete genomic sequence of 7081 nucleotides. Phylogenetic analysis based on the polyprotein and the VP1 genes indicated that it belonged to genotype PTV-4, whereas recombination analysis revealed that PTV-SCgz-01 is a natural recombinant with parental strains derived from HNMY (PTV-4) and China/SWU-ZG2/2018 (PTV-6). Experimental infection of 17-day-old Tibetan piglets demonstrated that this isolate induces severe watery diarrhea. Notably, the virus also caused severe pulmonary hemorrhage and mild cerebral hyperemia with neuronal degeneration, and it had a high mortality rate (40%), suggesting that strain PTV-SCgz-01 has strong pathogenic potential for 17-day-old Tibetan piglets. Our findings provide a more comprehensive molecular epidemiology of PTVs in Tibetan pigs and underscore the need for viral surveillance and control in this unique pig population.

Animals

Integrative Genomic, Transcriptomic and Epigenomic Analysis Reveals cis-regulatory Contributions to High-altitude Adaptation in Tibetan Pigs.

The Qinghai-Tibet Plateau, characterized by its extreme environmental conditions, presents significant challenges to life, making it an ideal region for studying adaptation and evolution. Tibetan pigs, known for their high genetic diversity and exceptional adaptability to high altitudes, serve as excellent models for investigating high-altitude adaptation. While previous studies have extensively identified genetic determinants associated with high-altitude adaptation, the molecular mechanisms, particularly cis-regulatory patterns, remain poorly understood. Here, we conducted a selective sweep analysis using 484 genomes from Chinese and Western pig breeds across various altitudes, revealing 38.56 Mb of genomic regions under selection in Tibetan pigs. Enrichment analysis identified the lung as the primary functional tissue involved in high-altitude adaptation, supported by tissue-specific transcriptional and regulatory patterns observed between Tibetan and Meishan pigs (low altitude). By integrating genomic, RNA-seq, ATAC-seq, and H3K27ac HiChIP data, we constructed comprehensive enhancer-promoter regulatory maps of candidate genes and pinpointed promising genetic determinants associated with high-altitude adaptation, including SNPs in EPAS1, KLF13, SPRED1, and CFD. These loci were predicted to influence chromatin accessibility and the interactions of regulatory elements, with altered binding strength of relevant transcription factors. Further in vitro experiments confirmed that these loci function as allele-specific enhancers, modulating the expression of target genes. Our findings elucidate the regulatory basis of high-altitude adaptation in Tibetan pigs and provide valuable insights for exploring hypoxia-related diseases in livestock and humans.

Animals