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Cited by 84Animal Virus Infections StudiesSARS-CoV-2 and COVID-19 Researchinterferon and immune responses

C eacam1a−/−Mice Are Completely Resistant to Infection by Murine Coronavirus Mouse Hepatitis Virus A59

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Hemmila, Erin, Turbide, Claire, Olson, Melanie, Jothy, Serge, Holmes, Kathryn V., Beauchemin, Nicole·2004·Journal of Virology
DOI 10.1128/jvi.78.18.10156-10165.2004PMC PMC515023
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Abstract

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.

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  • Rodent coronavirus MHV passes from nose to bulb even though rodent olfactory sensory neurons do not express Ceacam1, the main MHV receptor.

    “The rodent coronavirus MHV passes from the nose to the bulb, even though rodent OSNs do not express Ceacam1, the main MHV receptor (61, 66) (Figures S4C, S5E, S6A), suggesting that CoVs in the nasal mucosa can reach the brain through mechanisms independent of axonal transport by sensory nerves; interestingly, OB dopaminergic juxtaglomerular cells express Ceacam1 (Fig. 7E), which likely supports”

    From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [66]

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  1. [26]Moller, M. J., R. Kammerer, F. Grunert, and S. von Kleist. 1996. Biliary glycoprotein (BGP) expression on T cells and on a natural-killer-cell sub-population. Int. J. Cancer 65:740-745. [DOI] [PubMed] [Google Scholar]

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Authors
Hemmila, E., Turbide, C., Olson, M., Jothy, S., Holmes, K. V., & Beauchemin, N.
Affiliations
  • Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado
  • McGill University (CA)
  • St. Michael's Hospital (CA)
Corresponding author
Beauchemin, Nicole
ORCID
Beauchemin, Nicole
Venue
Journal of Virology
Publisher
American Society for Microbiology
Published
2004-09-15
Volume
78
Issue
18
Pages
10156-10165
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
DOI
10.1128/jvi.78.18.10156-10165.2004
PMC
PMC515023
OpenAlex
W2149870176
Cited by
84
References
49
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 8
FWCI
11.29
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Journal of Virology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • McGill University
  • National Institutes of Health
  • Canadian Institutes of Health Research (42501)
  • National Institute of Allergy and Infectious Diseases (AI25231, R01AI025231)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
carcinoembryonic antigen family, mouse hepatitis virus A59, coronavirus receptor, knockout mice, virus resistance, liver injury, spinal cord demyelination, C57BL/6 mice, viral pathogenesis
MeSH terms
Animals, Base Sequence, Carcinoembryonic Antigen, DNA, Glycoproteins, Murine hepatitis virus, Hepatitis, Viral, Animal, Mice, Inbred C57BL, Receptors, Virus, Antigens, CD, Cell Adhesion Molecules, Mice, Knockout, Coronavirus Infections, Gene Targeting, Mice

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