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Murine gamma-herpesvirus 68 glycoprotein 150 protects against virus-induced mononucleosis: a model system for
J P Stewart1, N Micali, E J Usherwood
1Department of Veterinary Pathology, University of Edinburgh, UK. james.stewart@ed.ac.uk
Abstract:
Murine gamma-herpesvirus 68 (MHV-68) is a model for the study of the pathogenesis of gamma-herpesviruses. Epstein-Barr virus (EBV) is a highly related gamma-herpesvirus that causes significant disease in humans. The major membrane antigen gp350 of EBV is a candidate vaccine antigen for protection against EBV-related disease. An MHV-68 glycoprotein, gp150, has significant homology to EBV gp350. We have therefore used the MHV-68 gp150 to model the potential efficacy of EBV gp350 in protecting from virus-associated disease. A recombinant vaccinia virus expressing MHV-68 gp150 was constructed. This recombinant vaccinia virus was used to infect mice via the subcutaneous route. This vaccination resulted in production of MHV-68-neutralising antibodies. Mice were then challenged intra-nasally with MHV-68. MHV-68-associated mononucleosis was virtually abrogated in immunised mice. However, mice did establish MHV-68 latency. The results suggest that gp350 may be effective as an immunogen to prevent EBV-associated infectious mononucleosis in humans that are EBV-seronegative.
Insights
Murine gamma-herpesvirus 68 (MHV-68) gp150 vaccination protected mice from infectious mononucleosis. However, MHV-68 latency was still established, suggesting gp350 may prevent Epstein-Barr virus (EBV) infectious mononucleosis in EBV-seronegative individuals.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Murine gamma-herpesvirus 68 (MHV-68) serves as a model for studying gamma-herpesvirus pathogenesis.
- Epstein-Barr virus (EBV), a related gamma-herpesvirus, causes significant human diseases.
- The EBV major membrane antigen gp350 is a potential vaccine candidate.
Purpose of the Study:
- To model the potential efficacy of EBV gp350 as a vaccine antigen.
- To investigate the protective effects of MHV-68 gp150 against MHV-68 infection.
- To assess the impact of gp150 vaccination on MHV-68-associated disease and latency.
Main Methods:
- Construction of a recombinant vaccinia virus expressing MHV-68 gp150.
- Subcutaneous immunization of mice with the recombinant vaccinia virus.
- Intra-nasal challenge of immunized mice with MHV-68.
- Monitoring for MHV-68-associated mononucleosis and latency.
Main Results:
- Vaccination induced MHV-68-neutralizing antibodies in mice.
- MHV-68-associated mononucleosis was nearly eliminated in vaccinated mice.
- MHV-68 latency was successfully established in vaccinated mice, indicating incomplete protection.
Conclusions:
- MHV-68 gp150 vaccination effectively prevents acute MHV-68 disease.
- The findings suggest EBV gp350 could be an effective immunogen for preventing infectious mononucleosis in EBV-seronegative humans.
- Further research is needed to address the establishment of viral latency.