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Direct entry of rabies virus into the central nervous system without prior local replication
V Shankar1, B Dietzschold, H Koprowski
1Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104-4268.
Abstract:
Rabies virus pathogenesis was studied in a mouse model by inoculation of the masseter muscle. At different intervals, the masseter muscle, trigeminal ganglia, and brain were analyzed for virus-specific RNA with a polymerase chain reaction assay, which revealed that as early as 18 h postinfection (p.i.), virus-specific RNA was present in the trigeminal ganglia, and at 24 h p.i., viral RNA was identified in the brain stem. Analysis of the masseter muscle demonstrated virus at 1 h p.i. but no virus-specific RNA between 6 and 30 h p.i., indicating that virus invaded the nerve ending directly, without prior replication in the muscle. At 36 h p.i., viral RNA was detected again in the masseter muscle. Selective amplification of plus- and minus-strand RNA isolated from the masseter muscle at 96 h p.i. revealed that the majority of the rabies virus-specific RNA was in the positive sense, suggesting virus replication in muscle tissue during late stages of infection.
Insights
Rabies virus directly invades nerve endings in mice, bypassing initial muscle replication. Later stages show viral RNA in muscle, suggesting replication occurs after nerve invasion.
Area of Science:
- Virology
- Neuroscience
- Infectious Diseases
Background:
- Rabies virus is a significant global health concern.
- Understanding rabies virus pathogenesis is crucial for developing effective treatments.
- The initial stages of rabies virus infection, particularly at the inoculation site, require further elucidation.
Purpose of the Study:
- To investigate the early pathogenesis of rabies virus following inoculation of the masseter muscle in a mouse model.
- To determine the temporal and spatial dissemination of rabies virus from the inoculation site to the nervous system.
- To analyze the replication dynamics of rabies virus in muscle tissue.
Main Methods:
- Mice were inoculated with rabies virus in the masseter muscle.
- Virus-specific RNA was quantified using polymerase chain reaction (PCR) at various time points post-infection (p.i.).
- Analysis included masseter muscle, trigeminal ganglia, and brain tissue.
- Plus- and minus-strand RNA amplification was performed to assess viral replication.
Main Results:
- Virus-specific RNA was detected in the trigeminal ganglia as early as 18 hours p.i. and in the brain stem at 24 hours p.i.
- While virus was present in the masseter muscle at 1 hour p.i., viral RNA was absent between 6 and 30 hours p.i., suggesting direct nerve invasion.
- Viral RNA reappeared in the masseter muscle at 36 hours p.i., with a predominance of positive-sense RNA at 96 hours p.i., indicating muscle replication.
Conclusions:
- Rabies virus exhibits direct neuroinvasion from the inoculation site, bypassing initial muscle replication.
- Muscle tissue can support rabies virus replication during later stages of infection.
- These findings provide critical insights into the early dissemination and replication strategies of rabies virus.