Generation of recombinant herpes simplex virus type 1 to be used for automatic tract tracing

We generated two insertional beta-galactosidase (lacZ) expressing herpes simplex virus type 1 (HSV-1) with putative mutations in the UL41 or US5 open reading frames. Purified recombinants or wild-type HSV-1 were injected into the left adrenal gland of hamsters. Three days later, virus-infected neurons were visualized with immunohistochemistry in spinal cord sections from all infected hamsters. Neurons were also visualized with X-Gal histochemistry in spinal cord sections from hamsters infected with either of the recombinants but not with the wild-type virus. Insertional mutagenesis of the HSV-1 genome by lacZ did not disrupt the neurotropic properties of the virus. Both recombinant viruses transneuronally labelled the central nervous system (CNS) sympathoadrenal preganglionic neurons and may be useful for the study of synaptic organization of neural circuits. Successful transynaptic transmission of this marker gene into CNS neurons from a peripheral organ suggests that other foreign genes may also be delivered into CNS neurons using HSV-1.