Mouse hepatitis virus strain A59 and blocking antireceptor monoclonal antibody bind to the N-terminal domain of cellular receptor
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Updated: Oct 8, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
G S Dveksler1, M N Pensiero, C W Dieffenbach
1Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Abstract:
Mouse hepatitis virus (MHV) strain A59 uses as cellular receptors members of the carcinoembryonic antigen family in the immunoglobulin superfamily. Recombinant receptor proteins with deletions of whole or partial immunoglobulin domains were used to identify the regions of receptor glycoprotein recognized by virus and by antireceptor monoclonal antibody CC1, which blocks infection of murine cells. Monoclonal antibody CC1 and MHV-A59 virions bound only to recombinant proteins containing the entire first domain of MHV receptor. To determine which of the proteins could serve as functional virus receptors, receptor-negative hamster cells were transfected with recombinant deletion clones and then challenged with MHV-A59 virions. Receptor activity required the entire N-terminal domain with either the second or the fourth domain and the transmembrane and cytoplasmic domains. Recombinant proteins lacking the first domain or its C-terminal portion did not serve as viral receptors. Thus, like other virus receptors in the immunoglobulin superfamily, including CD4, poliovirus receptor, and intercellular adhesion molecule 1, the N-terminal domain of MHV receptor is recognized by the virus and the blocking monoclonal antibody.
Insights
Mouse hepatitis virus (MHV) uses carcinoembryonic antigen family proteins as cellular receptors. The N-terminal domain of the MHV receptor is crucial for viral binding and infection, as identified through recombinant protein studies.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Mouse hepatitis virus (MHV) strain A59 infection relies on cellular receptors from the carcinoembryonic antigen (CEA) family within the immunoglobulin superfamily.
- Understanding the specific domains of these receptors involved in viral interaction is key to developing antiviral strategies.
Purpose of the Study:
- To identify the precise regions of the MHV receptor glycoprotein recognized by the virus and a blocking monoclonal antibody (CC1).
- To determine the essential domains for functional virus receptor activity.
Main Methods:
- Utilized recombinant receptor proteins with deletions in immunoglobulin domains.
- Transfected receptor-negative hamster cells with these recombinant clones.
- Assessed viral binding and infection following MHV-A59 challenge.
Main Results:
- Both MHV-A59 virions and monoclonal antibody CC1 specifically bound to recombinant receptors containing the complete first domain.
- Functional receptor activity required the N-terminal domain, along with either the second or fourth domain, and transmembrane/cytoplasmic domains.
- Recombinant proteins lacking the first domain or its C-terminal portion failed to mediate viral entry.
Conclusions:
- The N-terminal domain of the MHV receptor is recognized by both the virus and blocking antibodies, similar to other immunoglobulin superfamily receptors.
- This domain is essential for MHV binding and subsequent cellular infection.
