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Cell receptor-independent infection by a neurotropic murine coronavirus
T M Gallagher1, M J Buchmeier, S Perlman
1Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
Abstract:
The cellular receptors for a coronavirus, mouse hepatitis virus (MHV), have been recently identified as one or more members of the carcinoembryonic antigen (CEA) family. The neurotropic JHM strain of MHV (MHV-JHM) possesses a highly fusogenic surface (S) glycoprotein. This protein is now shown to promote the spread of MHV into cells lacking the specific CEA-related MHV receptor. Resistant cells are recruited into MHV-induced syncytium with consequent production of progeny virus. Cell-to-cell spread of virus via membrane fusion without the requirement for specific cell surface receptor offers a novel way for virus to spread within infected hosts.
Insights
Mouse hepatitis virus (MHV) spreads to resistant cells via membrane fusion, independent of specific receptors. This novel mechanism, driven by the MHV-JHM S glycoprotein, facilitates virus dissemination within hosts.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Mouse hepatitis virus (MHV) is a coronavirus.
- Cellular receptors for MHV, including the carcinoembryonic antigen (CEA) family, have been identified.
- The neurotropic JHM strain of MHV (MHV-JHM) has a highly fusogenic surface (S) glycoprotein.
Purpose of the Study:
- To investigate the mechanism of MHV-JHM spread into cells lacking specific CEA-related receptors.
- To determine the role of the MHV-JHM S glycoprotein in mediating cell-to-cell spread.
- To identify novel pathways for coronavirus dissemination.
Main Methods:
- Cell culture experiments using MHV-JHM.
- Analysis of viral spread in receptor-deficient cells.
- Characterization of the MHV-JHM S glycoprotein's fusogenic properties.
Main Results:
- The MHV-JHM S glycoprotein promotes MHV entry into cells lacking specific CEA-related receptors.
- Resistant cells are incorporated into MHV-induced syncytia, leading to progeny virus production.
- Cell-to-cell spread occurs via membrane fusion, bypassing the need for specific cell surface receptors.
Conclusions:
- MHV can spread through a novel mechanism involving cell-to-cell membrane fusion, independent of specific cellular receptors.
- The fusogenic S glycoprotein of MHV-JHM plays a critical role in this alternative dissemination pathway.
- This finding offers new insights into coronavirus pathogenesis and host-virus interactions.