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Journal of Virology, September 2004, p. 10156-10165, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.10156-10165.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Ceacam1a–/– Mice Are Completely Resistant to Infection by Murine Coronavirus Mouse Hepatitis Virus A59

Erin Hemmila,1 Claire Turbide,2 Melanie Olson,2 Serge Jothy,3 Kathryn V. Holmes,1,{dagger} and Nicole Beauchemin2,4*,{dagger}

Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado,1 McGill Cancer Centre,2 Departments of Biochemistry, Medicine, and Oncology, McGill University, Montreal, Quebec,4 Department of Laboratory Medicine and Pathobiology, St-Michael's Hospital, Toronto, Ontario, Canada3

Received 29 December 2003/ Accepted 10 May 2004

CEACAM1a glycoproteins are members of the immunoglobulin (Ig) superfamily and the carcinoembryonic antigen family. Isoforms expressing either two or four alternatively spliced Ig-like domains in mice have been found in a number of epithelial, endothelial, or hematopoietic tissues. CEACAM1a functions as an intercellular adhesion molecule, an angiogenic factor, and a tumor cell growth inhibitor. Moreover, the mouse and human CEACAM1a proteins are targets of viral or bacterial pathogens, respectively, including the murine coronavirus mouse hepatitis virus (MHV), Haemophilus influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis, as well as Moraxella catarrhalis in humans. We have shown that targeted disruption of the Ceacam1a (MHVR) gene resulting in a partial ablation of the protein in mice (p/p mice) led to reduced susceptibility to MHV-A59 infection of the modified mice in the BALB/c background. We have now engineered and produced a Ceacam1a–/– mouse that exhibits complete ablation of the CEACAM1a protein in every tissue where it is normally expressed. We report that 3-week-old Ceacam1a–/– mice in the C57BL/6 genetic background are fully resistant to MHV-A59 infection by both intranasal and intracerebral routes. Whereas virus-inoculated wild-type +/+ C57BL/6 mice showed profound liver damage and spinal cord demyelination under these conditions, Ceacam1a–/– mice displayed normal livers and spinal cords. Virus was recovered from liver and spinal cord tissues of +/+ mice but not of –/– mice. These results indicate that CEACAM1a is the sole receptor for MHV-A59 in both liver and brain and that its deletion from the mouse renders the mouse completely resistant to infection by this virus.


* Corresponding author. Mailing address: McGill Cancer Centre, McGill University, McIntyre Medical Sciences Building, 3655 Promenade Sir-William-Osler, Montreal, Quebec, Canada H3G 1Y6. Phone: (514) 398-3541. Fax: (514) 398-6769. E-mail: nicole.beauchemin{at}mcgill.ca.

{dagger} K.V.H. and N.B. contributed equally to this work.


Journal of Virology, September 2004, p. 10156-10165, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.10156-10165.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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