Mechanisms of bovine Hunnivirus entry into MDBK cells.

Bovine Hunnivirus is a non-enveloped, positive-sense, single-stranded RNA virus belonging to the genus Hunnivirus (family Picornaviridae). Its detection in various animal hosts worldwide suggests the potential for interspecies transmission. The first bovine Hunnivirus strain, BufHuV-GX-2106, was isolated from buffalo diarrheic feces. However, the pathogenic role of Hunnivirus in bovine hosts remains poorly understood. Here, we investigated the entry mechanisms of bovine Hunnivirus into MDBK cells. Our findings indicate that the virus enters MDBK cells via clathrin-mediated endocytosis and macropinocytosis, but not via caveolin-mediated endocytosis. Macropinocytosis depends on the Na⁺/H⁺ exchanger (NHE), phosphatidylinositol 3-kinase (PI3K), and receptor tyrosine kinases (RTKs). This study provides a foundation for understanding Hunnivirus pathogenesis and identifies potential targets for antiviral drug development.