MOUSE SUSCEPTIBILITY TO MOUSE HEPATITIS-VIRUS INFECTION IS LINKED TO VIRAL RECEPTOR GENOTYPE

We have reported that the receptor for mouse hepatitis virus (MHV) exp ressed in MHV-susceptible BALB/c mice (MHVR1) has 10 to 30 times the v irus-binding activity of the MHV receptor expressed in MHV-resistant S JL mice (MHVR2) (N. Ohtsuka, Y. K. Yamada, and F. Taguchi, J. Gen. Vir ol. 77:1683-1992, 1996). This fact indicates the possibility that the difference in MHV susceptibility between BALB/c and SJL mice is determ ined by the virus-binding activity of the receptor. To test this possi bility, we have examined MHV susceptibility in mice with the homozygou s MHVR1 gene (R1/R1 genotype), mice with the MHVR1 and MHVR2 genes (R1 /R2 genotype), and mice with the homozygous MHVR2 gene (R2/R2 genotype ) produced by cross and backcross mating between BALB/c and SJL mice. All 63 F-2 and backcrossed mice with the MHVR1 gene (R1/R1 and R1/R2) were susceptible to MHV infection, and all 57 with the homozygous MHVR 2 gene (R2/R2) were resistant. We have also examined the MHV receptor genotypes of several mouse strains that were reported to be susceptibl e to MHV infection, All of those mice had the MHVR1 gene. These result s suggest the possibility that the viral receptor determines the susce ptibility of the whole animal to MHV infection.