Experimental intranasal infection reveals broad tissue tropism of bovine coronavirus

Bovine coronavirus (BCoV) causes neonatal calf diarrhea, winter dysentery, and respiratory disease worldwide. However, its primary replication site remains uncertain, and systemic studies on tissue tropism are limited. We, therefore, intranasally inoculated colostrum-fed Holstein calves (6-13-day-old) with a BCoV isolate derived from diarrheic calf, and monitored clinical signs, gross and histopathological lesions, antigen distribution, and viral replication in multiple tissues. All calves were seropositive before challenge. Infected animals developed diarrhea without respiratory manifestations. Viral RNA appeared first in nasal swabs and subsequently in feces, yet viral load in nasal secretions was not associated with clinical signs. Apart from enlargement of the mesenteric lymph nodes, no characteristic gross lesions were observed. Digital RT-PCR and immunohistochemistry detected BCoV in tonsil, trachea, lung, liver, kidney, abomasum, and both small and large intestines, indicating epithelial tropism at each site. Although the inoculum originated from a diarrheic calf, histopathology revealed enteritis, mild interstitial pneumonia, tonsillitis, and hepatitis. These data indicate that BCoV initiates replication in respiratory epithelia and subsequently disseminates to the digestive tract, with no correlation between gross pathology and viral detection. We conclude that BCoV exhibits broad tissue tropism and may contribute to disorders beyond classical respiratory and enteric disease, thereby refining the current understanding of BCoV pathogenesis.