Background: The receptor for the murine coronavirus mouse hepatitis virus (MHV)-A59, called MHVR or Bgp1a, is a glycoprotein in the carcinoembryonic antigen family of the Ig superfamily. Biliary glycoprotein (Bgp) isoforms play a role in cell adhesion, bile acid transport, and ecto-ATPase activity. MHV-resistant SJL/J mice express a different allele of Bgp1 called Bgp1b. Analysis of the tissue and cellular distribution of Bgp1 proteins can therefore provide new insight on both cellular functions and MHV-A59--induced pathogenesis.
Experimental design: Bgp1 expression was analyzed in the digestive, respiratory, endocrine, urinary, and central nervous systems of adult BALB/c and SJL/J mice by immunocytochemistry and immunoelectron microscopy using a monoclonal Ab specific for the N-terminal domain of the Bgp1a proteins and polyclonal rabbit anti-Bgp1, which recognizes both the Bgp1a and Bgp1b proteins. The function of Bgp1 proteins as viral receptors was tested on tissue sections by a virus binding assay. MHV-A59 replication was analyzed by immunocytochemistry.
Results: Bgp1 expression was observed on membranes of epithelial cells (including hepatocytes, intestinal, endocrine, and respiratory epithelial cells), kidney proximal tubules, and endothelial cells in many tissues. It was usually localized at the apical pole of the cells and, when present, on the brush borders and the cilia. A new direct virus binding assay showed that MHV attachment onto cells correlates with Bgp1 expression. Viral infection was detected in hepatocytes, lymphoid tissue, and the exocrine pancreas but not in endocrine cells, enterocytes, kidney, or respiratory cells. In the central nervous system, no immunolabeling of neurons or glial cells was found with anti-Bgp1 Ab.
Conclusions: Bgp1 proteins are present on BALB/c and SJL/J epithelia and endothelia. These glycoproteins might be involved in cell-to-cell contacts, for example between hepatocytes. On BALB/c mice, Bgp1a expression is consistent with the tropism of MHV-A59 for the liver. However, Bgp1a was also expressed on cells that were not infected by MHV-A59.