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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Jul 1;88(13):5533–5536. doi: 10.1073/pnas.88.13.5533

Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins.

R K Williams 1, G S Jiang 1, K V Holmes 1
PMCID: PMC51911  PMID: 1648219

Abstract

The receptor for mouse hepatitis virus (MHV), a murine coronavirus, is a 110- to 120-kDa glycoprotein on intestinal brush border membranes and hepatocyte membranes. The N-terminal 25-amino acid sequence of immunoaffinity-purified MHV receptor was identical to the predicted mature N termini of two mouse genes related to human carcinoembryonic antigen (CEA) and was strongly homologous to the N termini of members of the CEA family in humans and rats. Polyclonal antibodies to human CEA recognized the immunoaffinity-purified MHV receptor and the MHV receptor in liver membranes and intestinal brush border membranes from MHV-susceptible mouse strains. In membranes from MHV-resistant SJL/J mice, the anti-CEA antibodies recognized a homologous glycoprotein that failed to bind MHV. The MHV receptor glycoprotein was detected in membranes of BALB/c colon, small intestine, and liver, which are the principal targets for MHV replication in vivo. The MHV receptor glycoprotein resembled members of the human CEA family in molecular weight, acidic pI, extensive glycosylation, solubility in perchloric acid, and tissue distribution. Thus, the MHV receptor is, to our knowledge, the first member of the CEA family of glycoproteins to be identified as a virus receptor.

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Selected References

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  1. Barnett T. R., Kretschmer A., Austen D. A., Goebel S. J., Hart J. T., Elting J. J., Kamarck M. E. Carcinoembryonic antigens: alternative splicing accounts for the multiple mRNAs that code for novel members of the carcinoembryonic antigen family. J Cell Biol. 1989 Feb;108(2):267–276. doi: 10.1083/jcb.108.2.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barthold S. W., Beck D. S., Smith A. L. Mouse hepatitis virus nasoencephalopathy is dependent upon virus strain and host genotype. Arch Virol. 1986;91(3-4):247–256. doi: 10.1007/BF01314284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beauchemin N., Benchimol S., Cournoyer D., Fuks A., Stanners C. P. Isolation and characterization of full-length functional cDNA clones for human carcinoembryonic antigen. Mol Cell Biol. 1987 Sep;7(9):3221–3230. doi: 10.1128/mcb.7.9.3221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benchimol S., Fuks A., Jothy S., Beauchemin N., Shirota K., Stanners C. P. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell. 1989 Apr 21;57(2):327–334. doi: 10.1016/0092-8674(89)90970-7. [DOI] [PubMed] [Google Scholar]
  5. Boyle J. F., Weismiller D. G., Holmes K. V. Genetic resistance to mouse hepatitis virus correlates with absence of virus-binding activity on target tissues. J Virol. 1987 Jan;61(1):185–189. doi: 10.1128/jvi.61.1.185-189.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  7. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. GOLD P., FREEDMAN S. O. DEMONSTRATION OF TUMOR-SPECIFIC ANTIGENS IN HUMAN COLONIC CARCINOMATA BY IMMUNOLOGICAL TOLERANCE AND ABSORPTION TECHNIQUES. J Exp Med. 1965 Mar 1;121:439–462. doi: 10.1084/jem.121.3.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Greve J. M., Davis G., Meyer A. M., Forte C. P., Yost S. C., Marlor C. W., Kamarck M. E., McClelland A. The major human rhinovirus receptor is ICAM-1. Cell. 1989 Mar 10;56(5):839–847. doi: 10.1016/0092-8674(89)90688-0. [DOI] [PubMed] [Google Scholar]
  10. Hinoda Y., Neumaier M., Hefta S. A., Drzeniek Z., Wagener C., Shively L., Hefta L. J., Shively J. E., Paxton R. J. Molecular cloning of a cDNA coding biliary glycoprotein I: primary structure of a glycoprotein immunologically crossreactive with carcinoembryonic antigen. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6959–6963. doi: 10.1073/pnas.85.18.6959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  12. Knobler R. L., Linthicum D. S., Cohn M. Host genetic regulation of acute MHV-4 viral encephalomyelitis and acute experimental autoimmune encephalomyelitis in (BALB/cKe x SJL/J) recombinant-inbred mice. J Neuroimmunol. 1985 Apr;8(1):15–28. doi: 10.1016/S0165-5728(85)80044-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kodelja V., Lucas K., Barnert S., von Kleist S., Thompson J. A., Zimmermann W. Identification of a carcinoembryonic antigen gene family in the rat. Analysis of the N-terminal domains reveals immunoglobulin-like, hypervariable regions. J Biol Chem. 1989 Apr 25;264(12):6906–6912. [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Lin S. H., Guidotti G. Cloning and expression of a cDNA coding for a rat liver plasma membrane ecto-ATPase. The primary structure of the ecto-ATPase is similar to that of the human biliary glycoprotein I. J Biol Chem. 1989 Aug 25;264(24):14408–14414. [PubMed] [Google Scholar]
  16. Lin S. H. Localization of the ecto-ATPase (ecto-nucleotidase) in the rat hepatocyte plasma membrane. Implications for the functions of the ecto-ATPase. J Biol Chem. 1989 Aug 25;264(24):14403–14407. [PubMed] [Google Scholar]
  17. Matsudaira P. Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J Biol Chem. 1987 Jul 25;262(21):10035–10038. [PubMed] [Google Scholar]
  18. Mendelsohn C. L., Wimmer E., Racaniello V. R. Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell. 1989 Mar 10;56(5):855–865. doi: 10.1016/0092-8674(89)90690-9. [DOI] [PubMed] [Google Scholar]
  19. Neumaier M., Zimmermann W., Shively L., Hinoda Y., Riggs A. D., Shively J. E. Characterization of a cDNA clone for the nonspecific cross-reacting antigen (NCA) and a comparison of NCA and carcinoembryonic antigen. J Biol Chem. 1988 Mar 5;263(7):3202–3207. [PubMed] [Google Scholar]
  20. Paxton R. J., Mooser G., Pande H., Lee T. D., Shively J. E. Sequence analysis of carcinoembryonic antigen: identification of glycosylation sites and homology with the immunoglobulin supergene family. Proc Natl Acad Sci U S A. 1987 Feb;84(4):920–924. doi: 10.1073/pnas.84.4.920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rooney B. C., Horne C. H., Hardman N. Molecular cloning of a cDNA for human pregnancy-specific beta 1-glycoprotein:homology with human carcinoembryonic antigen and related proteins. Gene. 1988 Nov 30;71(2):439–449. doi: 10.1016/0378-1119(88)90061-3. [DOI] [PubMed] [Google Scholar]
  22. Smith A. L., Cardellichio C. B., Winograd D. F., de Souza M. S., Barthold S. W., Holmes K. V. Monoclonal antibody to the receptor for murine coronavirus MHV-A59 inhibits viral replication in vivo. J Infect Dis. 1991 Apr;163(4):879–882. doi: 10.1093/infdis/163.4.879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Smith M. S., Click R. E., Plagemann P. G. Control of mouse hepatitis virus replication in macrophages by a recessive gene on chromosome 7. J Immunol. 1984 Jul;133(1):428–432. [PubMed] [Google Scholar]
  24. Staunton D. E., Merluzzi V. J., Rothlein R., Barton R., Marlin S. D., Springer T. A. A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses. Cell. 1989 Mar 10;56(5):849–853. doi: 10.1016/0092-8674(89)90689-2. [DOI] [PubMed] [Google Scholar]
  25. Streydio C., Lacka K., Swillens S., Vassart G. The human pregnancy-specific beta 1-glycoprotein (PS beta G) and the carcinoembryonic antigen (CEA)-related proteins are members of the same multigene family. Biochem Biophys Res Commun. 1988 Jul 15;154(1):130–137. doi: 10.1016/0006-291x(88)90660-2. [DOI] [PubMed] [Google Scholar]
  26. Sturman L. S., Holmes K. V. The molecular biology of coronaviruses. Adv Virus Res. 1983;28:35–112. doi: 10.1016/S0065-3527(08)60721-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Svenberg T., Hammarström S., Hedin A. Purification and properties of biliary glycoprotein I (BGP I). Immunochemical relationship to carcinoembryonic antigen. Mol Immunol. 1979 Apr;16(4):245–252. doi: 10.1016/0161-5890(79)90063-4. [DOI] [PubMed] [Google Scholar]
  28. Tawaragi Y., Oikawa S., Matsuoka Y., Kosaki G., Nakazato H. Primary structure of nonspecific crossreacting antigen (NCA), a member of carcinoembryonic antigen (CEA) gene family, deduced from cDNA sequence. Biochem Biophys Res Commun. 1988 Jan 15;150(1):89–96. doi: 10.1016/0006-291x(88)90490-1. [DOI] [PubMed] [Google Scholar]
  29. Thompson J. A., Pande H., Paxton R. J., Shively L., Padma A., Simmer R. L., Todd C. W., Riggs A. D., Shively J. E. Molecular cloning of a gene belonging to the carcinoembryonic antigen gene family and discussion of a domain model. Proc Natl Acad Sci U S A. 1987 May;84(9):2965–2969. doi: 10.1073/pnas.84.9.2965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tomassini J. E., Graham D., DeWitt C. M., Lineberger D. W., Rodkey J. A., Colonno R. J. cDNA cloning reveals that the major group rhinovirus receptor on HeLa cells is intercellular adhesion molecule 1. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4907–4911. doi: 10.1073/pnas.86.13.4907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Turbide C., Rojas M., Stanners C. P., Beauchemin N. A mouse carcinoembryonic antigen gene family member is a calcium-dependent cell adhesion molecule. J Biol Chem. 1991 Jan 5;266(1):309–315. [PubMed] [Google Scholar]
  33. Wege H., Siddell S., ter Meulen V. The biology and pathogenesis of coronaviruses. Curr Top Microbiol Immunol. 1982;99:165–200. doi: 10.1007/978-3-642-68528-6_5. [DOI] [PubMed] [Google Scholar]
  34. White J. M., Littman D. R. Viral receptors of the immunoglobulin superfamily. Cell. 1989 Mar 10;56(5):725–728. doi: 10.1016/0092-8674(89)90674-0. [DOI] [PubMed] [Google Scholar]
  35. Williams R. K., Jiang G. S., Snyder S. W., Frana M. F., Holmes K. V. Purification of the 110-kilodalton glycoprotein receptor for mouse hepatitis virus (MHV)-A59 from mouse liver and identification of a nonfunctional, homologous protein in MHV-resistant SJL/J mice. J Virol. 1990 Aug;64(8):3817–3823. doi: 10.1128/jvi.64.8.3817-3823.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Williams R. K., Kelly P. T., Akeson R. A. Cell-surface antigens of developing rat cerebellar neurons: identification with monoclonal antibodies. Brain Res. 1985 Apr;351(2):253–266. doi: 10.1016/0165-3806(85)90197-x. [DOI] [PubMed] [Google Scholar]

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