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Mutations associated with viral sequences isolated from mice persistently infected with MHV-JHM
J O Fleming1, C Adami, J Pooley
1Department of Neurology, University of Wisconsin School of Medicine, Madison, USA.
Abstract:
Mouse hepatitis virus JHM (JHMV or MHV-4) induces subacute and chronic demyelination in rodents and has been studied as a model human demyelinating diseases, such a multiple sclerosis. However, despite intensive investigation, the state of JHMV during chronic disease is poorly understood. Using reverse transcription-polymerase chain reaction amplification (RT-PCR) to "rescue" viral RNA, we have found that JHMV-specific sequences persist for at least 787 days after intracerebral inoculation of experimental mice. Analysis of persisting viral RNA reveals that it is extensively mutated, and we hypothesize that the mutations observed reflect adaptation of the viral quasispecies to low-level intracellular replication during chronic disease.
Insights
Mouse hepatitis virus (MHV) RNA persists in mice for over two years, showing extensive mutations. These mutations likely indicate viral adaptation during chronic demyelinating disease.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Mouse hepatitis virus JHM (JHMV) is a model for human demyelinating diseases like multiple sclerosis.
- The status of JHMV during the chronic phase of disease remains largely unknown.
Purpose of the Study:
- To investigate the persistence and genetic state of JHMV during chronic demyelination in a rodent model.
- To understand viral adaptation mechanisms in the context of persistent infection.
Main Methods:
- Utilizing reverse transcription-polymerase chain reaction (RT-PCR) to detect and amplify viral RNA.
- Analyzing viral RNA sequences from experimentally infected mice over an extended period (787 days).
Main Results:
- JHMV-specific RNA sequences were detected persisting in mice for at least 787 days post-inoculation.
- The persisting viral RNA exhibited extensive mutations compared to the original inoculum.
Conclusions:
- JHMV can persist in the central nervous system for prolonged periods during chronic disease.
- Viral RNA mutations suggest an adaptive evolutionary process, likely involving low-level intracellular replication, during chronic JHMV infection.