Organ tropism of murine coronavirus does not correlate with the expression levels of the membrane-anchored or secreted isoforms of the carcinoembryonic antigen-related cell adhesion molecule 1 receptor Free

Abstract

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is the sole known receptor of murine hepatitis virus (MHV) A59, but the available, often qualitative, data about CEACAM1 expression does not explain MHV organ tropism. transcripts undergo alternative splicing resulting in multiple isoforms, including secreted CEACAM1 isoforms that can neutralize the virus. We determined the quantities of transcripts encoding membrane-bound and secreted isoforms in mouse organs and a set of cell lines. , the lowest receptor mRNA levels were found in brain and muscle and these were similar to those in easily infectable cultured cells. While the quantities of the receptor transcripts varied between mouse organs, their abundance did not correlate with susceptibility to MHV infection. The proportion of transcripts encoding secreted isoforms also could not explain the selection of sites for virus replication, as it was constant in all organs. Our data suggest that neither of the two CEACAM1 isoforms defines MHV organ tropism.

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2012-09-01
2024-03-29
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References

  1. Barthold S. W., Smith A. L. 1984; Mouse hepatitis virus strain-related patterns of tissue tropism in suckling mice. Arch Virol 81:103–112 [View Article][PubMed]
    [Google Scholar]
  2. Beauchemin N., Draber P., Dveksler G., Gold P., Gray-Owen S., Grunert F., Hammarström S., Holmes K. V., Karlsson A. other authors 1999; Redefined nomenclature for members of the carcinoembryonic antigen family. Exp Cell Res 252:243–249 [View Article][PubMed]
    [Google Scholar]
  3. Bender S. J., Phillips J. M., Scott E. P., Weiss S. R. 2010; Murine coronavirus receptors are differentially expressed in the central nervous system and play virus strain-dependent roles in neuronal spread. J Virol 84:11030–11044 [View Article][PubMed]
    [Google Scholar]
  4. Blau D. M., Turbide C., Tremblay M., Olson M., Létourneau S., Michaliszyn E., Jothy S., Holmes K. V., Beauchemin N. 2001; Targeted disruption of the Ceacam1 (MHVR) gene leads to reduced susceptibility of mice to mouse hepatitis virus infection. J Virol 75:8173–8186 [View Article][PubMed]
    [Google Scholar]
  5. Budt M., Michely B., Müller M. M., Reutter W., Lucka L. 2002; Secreted CEACAM1 splice variants in rat cell lines and in vivo in rat serum. Biochem Biophys Res Commun 292:749–755 [View Article][PubMed]
    [Google Scholar]
  6. Chen Z., Chen L., Blumberg R. S. 2009; Editorial: CEACAM1: fine-tuned for fine-tuning. J Leukoc Biol 86:195–197 [View Article][PubMed]
    [Google Scholar]
  7. Dveksler G. S., Pensiero M. N., Cardellichio C. B., Williams R. K., Jiang G. S., Holmes K. V., Dieffenbach C. W. 1991; Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV. J Virol 65:6881–6891[PubMed]
    [Google Scholar]
  8. Dveksler G. S., Dieffenbach C. W., Cardellichio C. B., McCuaig K., Pensiero M. N., Jiang G. S., Beauchemin N., Holmes K. V. 1993; Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59. J Virol 67:1–8[PubMed]
    [Google Scholar]
  9. Gaur S., Shively J. E., Yen Y., Gaur R. K. 2008; Altered splicing of CEACAM1 in breast cancer: identification of regulatory sequences that control splicing of CEACAM1 into long or short cytoplasmic domain isoforms. Mol Cancer 7:46 [View Article][PubMed]
    [Google Scholar]
  10. Godfraind C., Langreth S. G., Cardellichio C. B., Knobler R., Coutelier J. P., Dubois-Dalcq M., Holmes K. V. 1995; Tissue and cellular distribution of an adhesion molecule in the carcinoembryonic antigen family that serves as a receptor for mouse hepatitis virus. Lab Invest 73:615–627[PubMed]
    [Google Scholar]
  11. Hammarström S. 1999; The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol 9:67–81 [View Article][PubMed]
    [Google Scholar]
  12. Han E., Phan D., Lo P., Poy M. N., Behringer R., Najjar S. M., Lin S. H. 2001; Differences in tissue-specific and embryonic expression of mouse Ceacam1 and Ceacam2 genes. Biochem J 355:417–423 [View Article][PubMed]
    [Google Scholar]
  13. Hemmila E., Turbide C., Olson M., Jothy S., Holmes K. V., Beauchemin N. 2004; Ceacam1a-/- mice are completely resistant to infection by murine coronavirus mouse hepatitis virus A59. J Virol 78:10156–10165 [View Article][PubMed]
    [Google Scholar]
  14. Hirai A., Ohtsuka N., Ikeda T., Taniguchi R., Blau D., Nakagaki K., Miura H. S., Ami Y., Yamada Y. K. other authors 2010; Role of mouse hepatitis virus (MHV) receptor murine CEACAM1 in the resistance of mice to MHV infection: studies of mice with chimeric mCEACAM1a and 1b. J Virol 84:6654–6666 [View Article][PubMed]
    [Google Scholar]
  15. Hundt S., Haug U., Brenner H. 2007; Blood markers for early detection of colorectal cancer: a systematic review. Cancer Epidemiol Biomarkers Prev 16:1935–1953 [View Article][PubMed]
    [Google Scholar]
  16. Ida-Hosonuma M., Iwasaki T., Yoshikawa T., Nagata N., Sato Y., Sata T., Yoneyama M., Fujita T., Taya C. other authors 2005; The alpha/beta interferon response controls tissue tropism and pathogenicity of poliovirus. J Virol 79:4460–4469 [View Article][PubMed]
    [Google Scholar]
  17. Kohaar I., Ploss A., Korol E., Mu K., Schoggins J. W., O’Brien T. R., Rice C. M., Prokunina-Olsson L. 2010; Splicing diversity of the human OCLN gene and its biological significance for hepatitis C virus entry. J Virol 84:6987–6994 [View Article][PubMed]
    [Google Scholar]
  18. Kuroki M., Arakawa F., Matsuo Y., Oikawa S., Nakazato H., Matsuoka Y. 1991; Three novel molecular forms of biliary glycoprotein deduced from cDNA clones from a human leukocyte library. Biochem Biophys Res Commun 176:578–585 [View Article][PubMed]
    [Google Scholar]
  19. Lavi E., Gilden D. H., Highkin M. K., Weiss S. R. 1986; The organ tropism of mouse hepatitis virus A59 in mice is dependent on dose and route of inoculation. Lab Anim Sci 36:130–135[PubMed]
    [Google Scholar]
  20. Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. 1986; The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 47:333–348 [View Article][PubMed]
    [Google Scholar]
  21. Öbrink B. 1997; CEA adhesion molecules: multifunctional proteins with signal-regulatory properties. Curr Opin Cell Biol 9:616–626 [View Article][PubMed]
    [Google Scholar]
  22. Öbrink B. 2008; On the role of CEACAM1 in cancer. Lung Cancer 60:309–312 [View Article][PubMed]
    [Google Scholar]
  23. Raaben M., Prins H. J., Martens A. C., Rottier P. J., De Haan C. A. 2009; Non-invasive imaging of mouse hepatitis coronavirus infection reveals determinants of viral replication and spread in vivo. Cell Microbiol 11:825–841 [View Article][PubMed]
    [Google Scholar]
  24. Rao P. V., Gallagher T. M. 1998; Intracellular complexes of viral spike and cellular receptor accumulate during cytopathic murine coronavirus infections. J Virol 72:3278–3288[PubMed]
    [Google Scholar]
  25. Sawicki S. G., Lu J. H., Holmes K. V. 1995; Persistent infection of cultured cells with mouse hepatitis virus (MHV) results from the epigenetic expression of the MHV receptor. J Virol 69:5535–5543[PubMed]
    [Google Scholar]
  26. Schickli J. H., Zelus B. D., Wentworth D. E., Sawicki S. G., Holmes K. V. 1997; The murine coronavirus mouse hepatitis virus strain A59 from persistently infected murine cells exhibits an extended host range. J Virol 71:9499–9507[PubMed]
    [Google Scholar]
  27. Schwanhäusser B., Busse D., Li N., Dittmar G., Schuchhardt J., Wolf J., Chen W., Selbach M. 2011; Global quantification of mammalian gene expression control. Nature 473:337–342 [View Article][PubMed]
    [Google Scholar]
  28. Simeone D. M., Ji B., Banerjee M., Arumugam T., Li D., Anderson M. A., Bamberger A. M., Greenson J., Brand R. E. other authors 2007; CEACAM1, a novel serum biomarker for pancreatic cancer. Pancreas 34:436–443 [View Article][PubMed]
    [Google Scholar]
  29. Singer B. B., Scheffrahn I., Öbrink B. 2000; The tumor growth-inhibiting cell adhesion molecule CEACAM1 (C-CAM) is differently expressed in proliferating and quiescent epithelial cells and regulates cell proliferation. Cancer Res 60:1236–1244[PubMed]
    [Google Scholar]
  30. Slobodskaya O., Laarman A., Spaan W. J. 2008; Intracellular restriction of a productive noncytopathic coronavirus infection. J Virol 82:451–460 [View Article][PubMed]
    [Google Scholar]
  31. Taguchi F., Hirai-Yuki A. 2012; Mouse hepatitis virus receptor as a determinant of the mouse susceptibility to MHV infection. Front Microbiol 3:68[PubMed] [CrossRef]
    [Google Scholar]
  32. Terahara K., Yoshida M., Taguchi F., Igarashi O., Nochi T., Gotoh Y., Yamamoto T., Tsunetsugu-Yokota Y., Beauchemin N., Kiyono H. 2009; Expression of newly identified secretory CEACAM1(a) isoforms in the intestinal epithelium. Biochem Biophys Res Commun 383:340–346 [View Article][PubMed]
    [Google Scholar]
  33. Vennema H., Heijnen L., Zijderveld A., Horzinek M. C., Spaan W. J. 1990; Intracellular transport of recombinant coronavirus spike proteins: implications for virus assembly. J Virol 64:339–346[PubMed]
    [Google Scholar]
  34. Versteeg G. A., Slobodskaya O., Spaan W. J. 2006; Transcriptional profiling of acute cytopathic murine hepatitis virus infection in fibroblast-like cells. J Gen Virol 87:1961–1975 [View Article][PubMed]
    [Google Scholar]
  35. Yokomori K., Lai M. M. 1992; The receptor for mouse hepatitis virus in the resistant mouse strain SJL is functional: implications for the requirement of a second factor for viral infection. J Virol 66:6931–6938[PubMed]
    [Google Scholar]
  36. Zhao L., Rose K. M., Elliott R., Van Rooijen N., Weiss S. R. 2011; Cell-type-specific type I interferon antagonism influences organ tropism of murine coronavirus. J Virol 85:10058–10068 [View Article][PubMed]
    [Google Scholar]
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