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Disease model: dissecting the pathogenesis of the measles virus
J B Patterson1, M Manchester, M B Oldstone
1Division of Virology, Dept of Neuropharmacology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
Abstract:
Host-pathogen interactions of measles virus (MV), a leading cause of childhood mortality worldwide, are still poorly understood. Using transgenic mice that express the human MV receptor CD46, we generated models to study the pathogenesis of MV infection of the central nervous system (CNS) and immune system. CNS infection in CD46 transgenic mice allows replication and spread throughout neurons, inflammation, and ultimately death of the animals. CD46-transgenic mice can also be used to study immunosuppression, a hallmark of measles. Together with mouse knockout technology and a system for generating recombinant MVs, CD46 transgenic mice will ultimately lead to a better understanding of both viral and host factors contributing to disease.
Insights
Measles virus (MV) pathogenesis remains unclear. New CD46 transgenic mouse models allow studying MV infection of the brain and immune system, revealing viral and host factors in disease.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Measles virus (MV) is a major global cause of childhood mortality.
- Understanding MV host-pathogen interactions, particularly in the central nervous system (CNS) and immune system, is crucial but limited.
- Existing models do not fully recapitulate the complex pathogenesis of MV infection.
Purpose of the Study:
- To develop and utilize transgenic mouse models for studying MV pathogenesis.
- To investigate MV infection within the CNS and its impact on the immune system.
- To elucidate the roles of viral and host factors in measles disease.
Main Methods:
- Generation of transgenic mice expressing the human measles virus receptor, CD46.
- Infection of CD46 transgenic mice with MV to model CNS and immune system pathology.
- Integration of mouse knockout technology and recombinant MV systems for comprehensive analysis.
Main Results:
- CD46 transgenic mice successfully model MV infection of the CNS, showing neuronal replication and spread.
- Observed inflammation and mortality in the CNS-infected mice, mirroring severe measles cases.
- Demonstrated the utility of these models for studying MV-induced immunosuppression.
Conclusions:
- CD46 transgenic mice provide valuable models for investigating measles virus pathogenesis.
- These models facilitate the study of MV's effects on the CNS and immune system.
- Future research with these models will enhance understanding of viral and host contributions to measles disease.