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

Abstract

In order to study the spread of poliovirus in the spinal cord of bonnet monkeys, 10(8) TCID50 Mahoney strain of poliovirus was inoculated into the ulnar nerves of monkeys that were subsequently autopsied on days 1, 2, 3, 6, 9, 12, 14, 15 and 16 postinoculation (p.i.). Virus spread in the spinal cord, the accompanying histopathological changes and paralysis occurred in a cervico-thoraco-lumbar direction. Virus reached the cervical region of the spinal cord within the first 3 days and subsequently spread to all segments of the spinal cord. In situ hybridization demonstrated viral RNA initially in the cervical neurons on day 3 p.i. and in the anterior horn neurons of lumbar segments of the spinal cord by day 6 p.i. Loss of Nissl substance in some of the anterior horn neurons was apparent on day 3 p.i. in the cervical and thoracic regions and by day 6 p.i. in the lumbar region. In the lumbar region, neuronophagia was a consistent feature which was observed on days 6-9 p.i., followed by neuronal dropouts on day 12 p.i. and thereafter. In the cervical and thoracic region, reappearance of Nissl substance was apparent from day 12 p.i. Upper limb paralysis preceded lower limb paralysis (5.5+/-1.73 vs 8.18+/-2.18, P = 0.046), further suggesting that virus spread within the spinal cord was via an intraneural route despite persistent viraemia detectable from day 2 p.i. onwards. The temporal distribution of the virus spread, distribution of viral RNA, histopathological and clinical changes indicate a cell-to-cell spread of poliovirus in the CNS, having gained access to the CNS from the peripheral nerve.