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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Glycoprotein M is an essential lytic replication protein of the murine gammaherpesvirus 68
Janet S May1, Susanna Colaco, Philip G Stevenson
1Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Abstract:
All herpesviruses encode a homolog of glycoprotein M (gM), which appears to function in virion morphogenesis. Despite its conservation, gM is inessential for the lytic replication of alphaherpesviruses. In order to address the importance of gM in gammaherpesviruses, we disrupted it in the murine gammaherpesvirus 68 (MHV-68). The mutant virus completely failed to propagate in normally permissive fibroblasts. The defective genome was rescued by either homologous recombination to restore the wild-type gM in situ or the insertion of an ectopic, intergenic expression cassette encoding gM into the viral genome. Thus, gM was essential for the lytic replication of MHV-68.
Insights
Glycoprotein M (gM) is essential for gammaherpesvirus replication. Disrupting gM in murine gammaherpesvirus 68 (MHV-68) prevented virus propagation, highlighting gM's critical role in the viral life cycle.
Area of Science:
- Virology
- Molecular Biology
- Herpesvirus Pathogenesis
Background:
- Herpesviruses share conserved genes, including glycoprotein M (gM), implicated in virion assembly.
- While gM is dispensable for alphaherpesvirus lytic replication, its role in gammaherpesviruses remains less understood.
Purpose of the Study:
- To investigate the essentiality of glycoprotein M (gM) for the lytic replication of gammaherpesviruses.
- To characterize the function of gM in murine gammaherpesvirus 68 (MHV-68) infection.
Main Methods:
- Genetic disruption of the gM gene in the murine gammaherpesvirus 68 (MHV-68) genome.
- Phenotypic analysis of the gM-deficient mutant in permissive fibroblast cell cultures.
- Viral genome rescue through homologous recombination and ectopic gene insertion.
Main Results:
- The MHV-68 gM mutant exhibited a complete failure to propagate in permissive fibroblasts.
- Restoration of wild-type gM via homologous recombination or ectopic expression rescued viral replication.
- These findings demonstrate gM's critical role in MHV-68 lytic cycle.
Conclusions:
- Glycoprotein M (gM) is essential for the lytic replication of murine gammaherpesvirus 68 (MHV-68).
- gM's function is crucial for gammaherpesvirus propagation, contrasting with its non-essential role in alphaherpesviruses.
- This study underscores the importance of gM in gammaherpesvirus pathogenesis and virion morphogenesis.
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