Morphological analysis of mouse hepatitis virus A59-induced pathology with regard to viral receptor expression.

Mouse hepatitis virus, strain A59 (MHV-A59), is a coronavirus that triggers in susceptible mice a wide variety of pathologies, including hepatitis, thymus involution, B lymphocyte polyclonal activation and, after intra-cerebral inoculation, transient demyelination. One receptor that mediates entry of the virus into target cells has been identified: it is a glycoprotein of the carcinoembryonic antigen family, called Bgp1a. The availability of antibodies recognizing this molecule permits the analysis of its cellular expression and of the relationship between receptor expression and pathology induced by the virus. Bgp1a is found on epithelial and endothelial cells as well as on B lymphocytes and macrophages. In the liver, Bgp1a expression correlates well with infection of hepatocytes and endothelial cells, leading to the development of hepatitis. However, other cells expressing this molecule, such as central nervous system endothelial cells, are not infected by the virus. This observation may explain how the blood-brain barrier prevents dissemination of MHV-A59 from the general circulation into the brain. Thymic atrophy results from apoptosis of immature double-positive T lymphocytes which might be caused indirectly by infection of a small proportion of thymus epithelial cells that express Bgp1a rather than by infection of T cells that do not express the receptor. Finally, polyclonal activation of B lymphocytes, leading to increased secretion of antibodies of the IgG2a isotype, involves a cascade of events, including cytokine secretion, that may result from the interaction of MHV-A59 with B cells and macrophages that express Bgp1a. Therefore, after viral infection, cellular expression of Bgp1a may have different results: cell lysis; alteration of cellular functions that may lead to indirect death of other cell types, or resistance to infection.