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Type 1 human poliovirus binds to human synaptosomes
Abstract:
Poliovirus is a neurotropic virus that selectively infects human motoneurons in vivo. The basis for the specificity of this infection is not fully understood. It has been suggested that this tropism occurs because motoneurons are the only neurons to express poliovirus receptors. We have examined this hypothesis by measuring the binding of 125I-labeled poliovirus type 1 to neural tissues. With this assay we have detected highly specific binding sites in human but not rodent neural tissue. Regional assays of binding in human central nervous system homogenates demonstrate that binding sites are not confined to motoneurons. Rather, they are widely distributed throughout the human neuraxis. Particularly in the forebrain, binding is more abundant in gray than white matter. For this reason, we performed tissue fractionation studies which indicate that poliovirus binding sites are enriched in synaptosomes, the subfraction of central nervous system gray matter tissue rich in synaptic endings. The preferential expression of poliovirus binding sites in synaptic endings may be an important factor in the motor tropism of this virus, inasmuch as the major category of neurons with synaptic endings outside the central nervous system are motoneurons; thus, particles of virus may preferentially bind to this cell type during poliovirus viremia.
Insights
Poliovirus selectively infects human motoneurons. Researchers found poliovirus binding sites are widespread in human neural tissue, particularly in synaptic endings, suggesting a new mechanism for motor neuron tropism.
Area of Science:
- Neurovirology
- Molecular Biology
- Immunology
Background:
- Poliovirus is a neurotropic virus that selectively infects human motoneurons.
- The precise mechanism behind this specific neuronal targeting remains unclear.
- A prevailing hypothesis suggests motoneurons are uniquely permissive due to poliovirus receptor expression.
Purpose of the Study:
- To investigate the distribution and localization of poliovirus binding sites in neural tissues.
- To test the hypothesis that poliovirus receptor expression is exclusive to motoneurons.
Main Methods:
- Utilized 125I-labeled poliovirus type 1 to measure viral binding to neural tissues.
- Conducted regional binding assays on human central nervous system homogenates.
- Performed tissue fractionation studies to identify enriched cellular compartments for poliovirus binding.
Main Results:
- Detected highly specific poliovirus binding sites in human, but not rodent, neural tissues.
- Found binding sites widely distributed throughout the human neuraxis, not limited to motoneurons.
- Demonstrated enrichment of poliovirus binding sites in synaptosomes, particularly in gray matter.
Conclusions:
- Poliovirus binding sites are not exclusive to motoneurons but are broadly distributed in human neural tissue.
- The enrichment of binding sites in synaptosomes suggests a significant role for synaptic endings in poliovirus tropism.
- Preferential binding to synaptic endings, especially those of motoneurons, may explain the virus's selective motor neuron infection.