Metavirome Identification and Pathogenicity Evaluation of Tibet Orbivirus in Pigs

Tibet orbivirus (TIBOV) is an orbivirus transmitted by mosquitoes and Culicoides, despite specific neutralizing antibodies being detected in pigs, but the molecular genetic characteristics of TIBOV strains in infected pigs are completely uncharted, and their pathogenicity in piglets is poorly elucidated. This study aimed to investigate the genetic characteristics of TIBOV in infected pigs and evaluate the pathogenicity of TIBOV in weaned piglets. Through viral metagenomic sequencing, seven segments (VP1-VP4, VP6, NS1, and NS2) of TIBOV were obtained from swine tissues, and the sequences showed high identity with TIBOVs isolated from Culicoides, mosquitos, and cattle. After infection with TIBOV, the body temperature, appetite, and behavior of the piglets were normal, whereas hemorrhage nodes were observed on the hooves of all piglets and on the abdominal skin of one pig. Viremia was first detected at 2 days postinfection (dpi), peaked at 6 dpi, and remained high until 21 dpi. The virus was distributed in multiple organs, and the highest viral load and strongest viral nucleic acid signals were observed in the spleen. The most severe lesion was observed in the spleen with white pulp atrophy, a decreased number of lymphocytes, and widened septa of the medullary cord, indicating that the spleen was the most important target organ of TIBOV infection. The levels of inflammatory cytokines, including interleukin (IL)-18, tumor necrosis factor-α (TNF-α), interferon (IFN)-α, and IFN-λ3 in peripheral blood lymphocytes decreased significantly from 2 to 6 dpi, and interferon-stimulated gene-15 (ISG-15) and IFN regulatory factor 7 (IRF-7) expression levels declined significantly from 2 to 9 dpi, suggesting that the host immune response was inhibited within 6 dpi. Our findings confirmed that TIBOV elicited long-term viremia with mild clinical symptoms in piglets, the spleen was the target organ of TIBOV proliferation, and the host immune response may be slightly inhibited in the early stage of viral infection.