Direction of transneuronal transport of herpes simplex virus 1 in the primate motor system is strain-dependent.

We examined the axonal transport of two strains of herpes simplex virus 1 (HSV-1) within the central nervous system of cebus monkeys. Each strain was injected into the "arm area" of the primary motor cortex. One strain, HSV-1(McIntyre-B), was transported transneuronally in the retrograde direction. It infected neurons at sites known to project to the arm area of the primary motor cortex (e.g., ventrolateral thalamus). In addition, "second-order" neurons were labeled in the deep cerebellar nuclei (dentate and interpositus) and in the globus pallidus (internal segment). This result supports the concept that the arm area of the primary motor cortex is a target of both cerebellar and basal ganglia output. In contrast, the other strain, HSV-1(H129), was transported transneuronally in the anterograde direction. It infected neurons at sites known to receive input from the arm area of the primary motor cortex (e.g., putamen, pontine nuclei). In addition, "third-order" neurons were labeled in the cerebellar cortex (granule and Golgi cells) and in the globus pallidus (largely the external segment). Our observations suggest that strain differences have an important impact on the direction of transneuronal transport of HSV-1. Furthermore, it should be possible to examine the organization of cerebellar and basal ganglia loops with cerebral cortex by exploiting transneuronal transport of HSV-1 and virus strain differences.