Clinical course of PPM in hPVR-tg mice infected with PV1(M). hPVR-tg mice of four experimental groups were infected with 5 × 10⁶ PFU of PV1(M) by the intravenous route. At defined intervals following virus inoculation (2 h, 6 h, 24 h, and 48 h p.i., indicated by vertical broken lines), animals of groups III and IV were treated with i.m. injections into the left gastrocnemius muscle (see Materials and Methods). All mice were observed for the appearance of neurological symptoms and clinically assessed according to the following scheme: 0, no symptoms; 1, general symptoms (ruffled fur and reduced activity); 2, paraparesis; 3, paraplegia and/or involvement of the upper extremities; 4, respiratory involvement; and 5, death. The average clinical scores for four mice are indicated. Mice that were treated with repeated i.m. injections developed more severe neurological symptoms earlier than animals of all other experimental groups. A sciatic nerve block prevented the accelerated course of PPM in mice treated with multiple i.m. injections. □, group I; ○, group II; ▪, group III; •, group IV.

Histopathological evaluation of PV-induced damage within the lumbosacral segments of the spinal cords of mice from experimental groups I (panels 1A to C), III (panels 2A to C), and IV (panels 3A to C). The results of histopathological analysis of tissue from mice of group II have been omitted because the pace of progression of spinal lesions was indistinguishable from that in group I. Spinal cord tissue specimens were obtained from mice sacrificed 48 h (panels A), 72 h (panels B), and 96 h (panels C) following virus inoculation and were processed as described previously (9). Mice that had not been treated with multiple i.m. injections developed minor signs of virus-induced lesions within 96 h p.i. (panel 1C; arrow indicates motor neurons with characteristic cytopathic changes). In contrast, the spinal cords of animals that had been treated with the regimen of i.m. injections displayed complete destruction of the motor neuron population only 72 h p.i. (panel 2B). The acceleration of the progression of spinal lesions caused by multiple i.m. injections could be prevented by implementing a neural block through monolateral sciatic nerve transection (compare panels 2A to C with panels 3A to C). Bar, 250 μm.

Implementation of the neural block. The sciatic nerve was severed, disconnecting its peripheral branches, the common peroneal and tibial nerves, from the spinal cord. Motoric and sensory innervation of the gastrocnemius muscle in the limb treated was thus interrupted.

Replication profiles of PV1(M) in tissues of hPVR-tg mice. Mice were sacrificed at the indicated time points following intravenous virus administration. (A) Replication rates in gastrocnemius muscle. Virus replication in uninjured skeletal muscle from all experimental groups was negligible (only values for groups I and II are shown). In animals that had received multiple i.m. injections injury of gastrocnemius muscle led to elevated titers of virus. (B) Virus growth in lumbosacral segments of the spinal cords of mice from group III was accelerated and significantly enhanced compared to virus propagation in controls and nerve-transected animals that had also been treated with multiple i.m. injections. (C) Viral replication in cervical segments was less divergent, with a slight lead in efficiency of virus replication in group III mice over their nerve-transected peers. ▪, groups I and II; •, group III; ○, group IV.