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Published on: February 3, 2012
Mouse hepatitis virus receptors: more than a single carcinoembryonic antigen
1Howard Hughes Medical Institute, University of Southern California School of Medicine, Los Angeles.
Abstract:
Mouse hepatitis virus (MHV), a murine coronavirus, has been shown to utilize carcinoembryonic antigen (CEA) as the receptor. We have demonstrated that MHV can utilize a different isoform of CEA, which is an alternatively spliced gene product that is expressed in different tissues, as a receptor. Furthermore, the CEA molecules from a resistant mouse strain (SJL) have different sequences and yet serve as functional viral receptors. Thus, MHV can use more than a single type of CEA molecule as the receptor. We have also shown that some mouse cell lines express functional CEA molecules and yet are resistant to infections by certain MHV strains. Biochemical studies of the infected cells indicate that MHV infections in these cell lines are blocked at the steps of virus entry. We conclude that MHV entry requires additional cellular factors other than CEA, the viral receptor. The significance of viral receptors and the additional cellular factors in regulating viral tropism is discussed.
Insights
Mouse hepatitis virus (MHV) uses different forms of carcinoembryonic antigen (CEA) as a receptor. However, MHV entry into cells also requires additional cellular factors beyond CEA.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Mouse hepatitis virus (MHV), a murine coronavirus, is known to use carcinoembryonic antigen (CEA) as its cellular receptor.
- Understanding viral entry mechanisms is crucial for developing antiviral strategies.
Purpose of the Study:
- To investigate the role of different carcinoembryonic antigen (CEA) isoforms and sequences in mouse hepatitis virus (MHV) infection.
- To identify additional cellular factors required for MHV entry beyond the viral receptor.
Main Methods:
- Utilizing different mouse strains and cell lines expressing various CEA isoforms.
- Performing biochemical studies to analyze virus-cell interactions and identify blockades in viral entry.
Main Results:
- MHV can utilize alternatively spliced CEA isoforms and CEA molecules with different sequences as functional viral receptors.
- Some cell lines expressing functional CEA are resistant to MHV infection, indicating entry is blocked.
- Biochemical analysis revealed that MHV entry is inhibited at post-receptor binding stages.
Conclusions:
- MHV tropism is regulated by multiple CEA variants and additional cellular factors.
- Viral entry into host cells is a complex process requiring more than just the primary viral receptor.
- Identifying these additional factors is key to understanding MHV pathogenesis and tropism.
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