Transneuronal transfer of herpes simplex virus type 1 (HSV 1) from mixed limb nerves to the CNS. I. Sequence of transfer from sensory, motor, and sympathetic nerve fibres to the spinal cord.

The time course of transneuronal transfer of Herpes simplex virus type 1 (HSV 1) from sensory, motor, and sympathetic nerve fibres to connected spinal neurones was examined. After injection of a constant number of infectious units into distal forelimb or hindlimb nerves of inbred rats of the same age, the extent of viral transfer was strictly dependent on the survival time postinoculation (p.i.). Retrograde transport to somatic motoneurones occurred at 28-29 hours p.i. (stage 1), in synchrony with anterograde transneuronal transfer via small cutaneous afferents (to laminae I-II). At 36-43 hours p.i. (stage 2), retrograde transneuronal transfer from sympathetic nerve fibres first labelled sympathetic preganglionic neurones. At 48-51 hours p.i. (stage 3), transfer via sensory and sympathetic axons became more extensive, labelling laminae III-IV and other preganglionic neurones. Transneuronal transfer from large muscle afferents and motoneurones (to Clarke's columns and the spinal intermediate zone) occurred only at 66-78 hours p.i. (stage 4). Further increases in distribution (stages 5-6) obtained between 78 and 97 hours p.i. may reflect both specific labelling of second and third order neurones and a gradual local loss of specificity. These results indicate that transfer of HSV 1 occurs through all main classes of peripheral axons, but that both anterograde and retrograde transneuronal transfer from small (unmyelinated and fine myelinated) cutaneous and sympathetic axons precedes transfer from large (myelinated) cutaneous and muscle afferents and motor axons. Analysis of viral transfer at sequential intervals is required to distinguish serially connected neurones, determine the route of labelling, and ensure its specificity.