Coronaviruses of mice and rats are a common cause of enzootic infections in colonies of laboratory rodents, frequently compromising research projects that depend upon these animals. Many different strains of mouse coronavirus (MHV) and rat coronavirus (RCV) infect specific organs or tissues in the animals, causing a variety of diseases such as respiratory or enteric infection, neurological disease, hepatitis, adenitis, or immune disorders. The applicant has identified a murine glycoprotein (MHVR) related to carcinoembryonic antigen (CEA) as a receptor for MHV-A59. CEA-related glycoproteins of mice and rats were cloned and expressed separately in cells of other species. Surprisingly, the applicant found that several different CEA-related glycoproteins can serve as alternative receptors for MHV-A59. In murine tissues, these receptors are expressed singly or together in a developmentally regulated way.The applicant will test the hypothesis that the tissue tropism and species specificity of various rodent coronavirus strains are determined in part by the relative effectiveness of the interactions between the virus attachment proteins and alternative receptors. Biosensor technology will be utilized to quantitatively compare binding of virus attachment proteins to alternative receptors, analyze changes in the viral protein and membrane that follow receptor binding, and determine the effects of virus mutations upon interactions with receptors. The synthesis and processing of receptor glycoproteins will be studied, and the genetics of receptor expression in tissues from mice of different strains and ages will be analyzed. in vitro models for receptor selection by different coronavirus strains will be developed, and the diseases causes by virus variants selected in vitro for altered receptor specificity will be studied. The rodent coronaviruses are a unique model for the role of receptor specificity in virus pathogenesis.
