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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
The murine gammaherpesvirus 68 ORF27 gene product contributes to intercellular viral spread
Janet S May1, Jennifer Walker, Susanna Colaco
1Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Abstract:
Herpesviruses remain predominantly cell associated within their hosts, implying that they spread between cells by a mechanism distinct from free virion release. We previously identified the efficient release of murine gammaherpesvirus 68 (MHV-68) virions as a function of the viral gp150 protein. Here we show that the MHV-68 ORF27 gene product, gp48, contributes to the direct spread of viruses from lytically infected to uninfected cells. Monoclonal antibodies to gp48 identified it on infected cell surfaces and in virions. gp48-deficient viruses showed no obvious deficit in virion cell binding, single-cycle replication, or virion release but had reduced lytic propagation between cells. After intranasal infection of mice, ORF27-deficient viruses were impaired predominantly in lytic replication in the lungs. There was a small deficit in latency establishment, but long-term latency appeared normal. Since ORF27 has homologs in both Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, it is likely part of a conserved mechanism employed by gammaherpesviruses to disseminate lytically in their hosts.
Insights
Murine gammaherpesvirus 68 (MHV-68) uses the gp48 protein to spread directly between cells. This viral protein is essential for efficient lytic replication in the lungs during infection.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Herpesviruses typically remain cell-associated, suggesting non-virion-mediated spread.
- Previous work identified murine gammaherpesvirus 68 (MHV-68) gp150's role in virion release.
Purpose of the Study:
- To investigate the role of MHV-68 ORF27 gene product, gp48, in viral dissemination.
- To determine gp48's contribution to cell-to-cell spread and lytic replication.
Main Methods:
- Generation of gp48-deficient MHV-68 viruses.
- Characterization of viral properties including cell binding, replication, and release.
- Monoclonal antibody analysis to detect gp48 on infected cells and virions.
- Intranasal infection model in mice to assess in vivo replication and latency.
Main Results:
- gp48-deficient MHV-68 showed no deficits in virion binding, replication, or release.
- A significant reduction in direct cell-to-cell spread was observed for gp48-deficient viruses.
- In vivo, ORF27-deficient viruses exhibited impaired lytic replication in the lungs.
- A minor deficit in initial latency establishment was noted, with normal long-term latency.
Conclusions:
- MHV-68 gp48 is crucial for direct cell-to-cell spread, distinct from virion release.
- The ORF27 gene product plays a significant role in MHV-68 lytic replication, particularly in the lungs.
- gp48 homologs in other gammaherpesviruses suggest a conserved dissemination mechanism.
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