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Distinct pathways of viral spread in the host determined by reovirus S1 gene segment
Abstract:
The genetic and molecular mechanisms that determine the capacity of a virus to utilize distinct pathways of spread in an infected host were examined by using reoviruses. Both reovirus type 1 and reovirus type 3 spread to the spinal cord following inoculation into the hindlimb or forelimb footpad of newborn mice. For type 3 this spread is through nerves and occurs via the microtubule-associated system of fast axonal transport. By contrast, type 1 spreads to the spinal cord through the bloodstream. With the use of reassortant viruses containing various combinations of double-stranded RNA segments (genes) derived from type 1 and type 3, the viral S1 double-stranded RNA segment was shown to be responsible for determining the capacity of reoviruses to spread to the central nervous system through these distinct pathways.
Insights
Reoviruses spread differently in mice: type 3 uses nerves, while type 1 uses the bloodstream. The S1 gene segment dictates this viral spread pathway to the central nervous system.
Area of Science:
- Virology
- Molecular Biology
- Neuroscience
Background:
- Viruses exhibit diverse spread mechanisms within hosts.
- Understanding viral tropism and spread is crucial for disease control.
- Reoviruses offer a model to study viral dissemination pathways.
Purpose of the Study:
- To investigate the genetic basis of distinct viral spread pathways.
- To identify the viral component responsible for neurotropism.
- To elucidate mechanisms of viral entry into the central nervous system.
Main Methods:
- Utilized reassortant reoviruses (type 1 and type 3) with mixed genetic segments.
- Inoculated newborn mice in the footpad and tracked viral spread to the spinal cord.
- Analyzed viral spread via neural (fast axonal transport) versus hematogenous routes.
Main Results:
- Reovirus type 3 spreads to the spinal cord via fast axonal transport through nerves.
- Reovirus type 1 spreads to the spinal cord through the bloodstream.
- The viral S1 double-stranded RNA segment was identified as the determinant of distinct spread pathways.
Conclusions:
- The S1 gene segment of reoviruses dictates tropism and spread to the central nervous system.
- Viral genetic makeup significantly influences the route of dissemination in the host.
- This finding provides insight into viral neuroinvasion mechanisms.