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.

Cell-to-cell spread of poliovirus in the spinal cord of bonnet monkeys (Macaca radiata).

“…Reappearance of Nissl substance in the cervical cord at a later time-point, indicative of neuronal recovery (Bodian, 1949), suggested that virus-cell interactions were different in the neurons at different anatomical sites. PVRs are distributed throughout the spinal cord (Brown et al, 1987). Since we found that virus replicated efficiently in both cervical and lumbar regions of the spinal cord, the difference in pathology may not be at the level of the receptor.…”

Monoclonal antibody identification of a 100-kDa membrane protein in HeLa cells and human spinal cord involved in poliovirus attachment.

“…Initial immunohistochemical studies suggest that the AF3 epitope is a synaptic antigen (data not shown). In addition, previous studies raise the possibility that poliovirus preferentially binds to synaptosomes (29). The functional role of the receptor site may provide insight into the neurotropism of poliovirus and unique properties of the neurons that are infected by poliovirus.…”

Molecular Pathogenicity of Enteroviruses Causing Neurological Disease

“…Clinical observations and animal models have revealed lesions within the CNS that indicate unique tissue tropisms for different enteroviruses. Poliovirus primarily affects the anterior horns of gray matter in the spinal cord, which are composed of motor neurons innervating skeletal muscle (Jubelt et al, 1980;Brown et al, 1987). Poliovirus receptors are highly expressed in synaptosomes and the neuromuscular junctions provide the most accessible sites outside the CNS for poliovirus binding (Brown et al, 1987).…”

“…Poliovirus primarily affects the anterior horns of gray matter in the spinal cord, which are composed of motor neurons innervating skeletal muscle (Jubelt et al, 1980;Brown et al, 1987). Poliovirus receptors are highly expressed in synaptosomes and the neuromuscular junctions provide the most accessible sites outside the CNS for poliovirus binding (Brown et al, 1987). Similarly, EV-D68 damages motor neurons of the anterior horn in the spinal cord and brain stem leading to lesions visible on the MRI within these structures .…”