Infectious mechanisms of enteropathogenic bovine coronaviruses

The primary disease mechanism in infections of calves with enteropathogenic bovine coronaviruses (BCV) involves cytocidal interaction with differentiated enterocytes. Cytopathic expression of BCV infection of cultured cells depends on the viral strain and the cell type. BCV-induced cell fusion occurred under neutral or alkaline but not acidic conditions. Lysosomotropic bases did not significantly reduce virus yield, suggesting that productive BCV infection was not mediated by endocytosis but rather by direct fusion of the viral envelope with the plasma membrane. Trypsin cleavage of the 185 kDa S glycoprotein into 100 and 110 kDa subunits was required for cell fusion and productive infection of cultured BFS cells with the cell-adapted, avirulent strain BCV-L9. This strain has a wide host cell range in vitro while several wild-type, virulent strains were restricted to HRT-18 cells. Antigenic and genomic comparisons of the avirulent and virulent strains revealed corresponding differences. Some monoclonal antibodies against S reacted with both virulent and avirulent strains, while others reacted only with the avirulent strain BCV-L9. Nucleotide sequences of the S genes indicated that amino acid substitutions in cleavage sites, antigenic regions, and putative fusion domains occurred and differentiated BCV strains.