Mouse Hepatitis Virus Receptor as a Determinant of the Mouse Susceptibility to MHV Infection

Taguchi, Fumihiro; Hirai-Yuki, Asuka

The N domain of CEACAM1 alone is sufficient to bind MHV; a soluble form consisting of the N domain alone works efficiently to bind to MHV (Dveksler et al., 1993a; Miura et al., 2004) . Also, the N domain alone can neutralize viruses and induce conformational change in the S protein. Moreover, the binding of the N domain to the S protein of MHV induces the fusion activation of the S protein (Taguchi and Matsuyama, 2002; Miura et al., 2004) . However, when the N domain alone is expressed on the membrane (which has both TM and Cy), this molecule fails to work as a functional receptor (Dveksler et al., 1993a; Miura et al., 2004) . This may be due to its short molecule that is buried among various cell surface molecules and thus fails to have a chance to attach to the virions (Dveksler et al., 1993a) . We have compared the virus-binding activity of CEACAM1a and CEACAM1b. Soluble CEACAM1a and CEACAM1b composed of N and A2 domains prepared on nitrocellulose paper were allowed to attach to an MHV virion (viral protein blot assay). By this method, CEACAM1a binds to virions more than 300-fold efficiently when compared with CEACAM1b (Ohtsuka et al., 1996) . We also examined the neutralization activity of the two soluble proteins, finding that, in this assay, CEACAM1a is highly reactive and neutralizes MHV more than 300-fold efficiently than does CEACAM1b. These results are in agreement with the observations of the Holmes lab (Boyle et al., 1987) . However, when those proteins are expressed in MHV-non-permissive BHK cells, CEACAM1a exhibits only a 10-to 30-fold higher receptor function when compared with that of CEACAM1b, and, again, this finding is similar to those obtained by the Holmes lab (Boyle et al., 1987) . Accordingly, from these findings, we concluded that the small difference in receptor function between CEACAM1a and CEACAM1b will be amplified after several viral growths, as also postulated by Holmes and her collaborators. As for the receptor binding site in the N domain of CEACAM1, Gallagher and coworkers reported six contiguous amino acids from 38 to 43 in the N domain different between CEACAM1a and CEACAM1b play an important role in the differences seen in receptor function (Rao et al., 1997) . Others showed that amino acids 34-52 are involved in virus-binding (Wessner et al., 1998) .