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

Taguchi, Fumihiro; Hirai-Yuki, Asuka

Holmes and co-workers tried to find a receptor protein by using susceptible BALB/c and resistant SJL/J mice (Boyle et al., 1987) . They prepared cell membrane fractions from MHV target tissues, intestines, and liver, of those mice and showed, by using a viral overlay protein blot assay (whereby virions bind to the protein on a membrane filter prepared by Western blotting), that BALB/c mice express a molecule of 110-120 kDa on cell membranes to bind MHV virus particles. However, in the same fraction of SJL mice, they failed to find the protein that would bind MHV (Boyle et al., 1987; Williams et al., 1990) . Accordingly, they speculated that the protein was a receptor for MHV and determines mouse susceptibility. Thereafter, they isolated the protein and analyzed the partial amino acid sequence of the protein, which suggested to them that the protein is similar to a carcinoembryonic antigen, CEA . They finally isolated a cDNA clone and identified the protein to be a biliary glycoprotein of the CEA family (Dveksler et al., 1991) , now called carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; Beauchemin et al., 1999) . The expression of this protein in non-permissive cells converted them into cells that were permissive to MHV infection, www.frontiersin.org a finding that indicated this protein serves as an MHV receptor (Dveksler et al., 1991) . These findings suggested to them that the susceptibility of the mouse to MHV infection is determined by the presence or absence of this molecule. Soon after these findings were published, they reported that the CEACAM1 counterpart is expressed in the SJL (Dveksler et al., 1993b) ; however, they also reported that the CEACAM1 counterpart found in SJL is also functional as a receptor for MHV when expressed in non-permissive cells, although the receptor functionality is less efficient compared with the CEACAM1 found in BALB/c (Dveksler et al., 1993b) . Holmes and co-workers explained that the relatively small difference in receptor function between BALB/c CEACAM1 and SJL CEACAM1 could result in the very large biological differences in the multiple cycle infections that are required to cause disease in animals (Dveksler et al., 1993b) . There is a slight difference in amino acid sequences between CEACAM1 found in most mouse strains and CEACAM1 expressed in SJL in the MHV-binding region (Rao et al., 1997; Beauchemin et al., 1999) ; these are allelic forms and called CEACAM1a for BALB/c type and CEACAM1b for SJL type (Beauchemin et al., 1999) . In contrast to the hypothesis by Holmes and co-workers, Yokomori and Lai (1992) expressed CEACAM1a derived from C57BL/6 and CEACAM1b from SJL mice in MHV-non-permissive cells and found no significant difference in viral growth between cells expressing CEACAM1a and those with CEACAM1b, which may mean that the susceptibility difference observed between those two mouse strains may not be attributable to MHV receptor protein.