Delivery of a foreign gene to sympathetic preganglionic neurons using recombinant herpes simplex virus

Two recombinant herpes simplex type 1 viruses expressing beta-galactosidase (encoded by the Escherichia coli lacZ gene) inserted into the unique long 41 (encoding virus host shutoff) or unique short 5 (encoding glycoprotein J) open reading frames were generated. Purified recombinants or wild-type herpes simplex type 1 were injected into the left adrenal gland of hamsters. Three days later, virus-infected neurons were detected in spinal cord sections from all infected hamsters. Neurons were visualized with beta-galactosidase histochemistry in spinal cord sections from hamsters infected with either of the recombinants but not with the wild-type virus. Wild-type virus could only be detected with immunocytochemistry. Insertional mutagenesis into the unique long 41 or unique short 5 regions of the herpes simplex genome by lacZ did not disrupt the neurotropic properties of the virus. Both recombinant viruses labelled the central nervous system sympathoadrenal preganglionic neurons as well as brainstem neurons. Because the virus host shutoff recombinant more readily crossed synapses to reach the brainstem compared to the glycoprotein J recombinant, the presence of glycoprotein J may facilitate cell to cell transmission in vivo. Both recombinants may be useful for the study of synaptic organization of neural circuits. Our recombinant viruses were less lytic yet neurovirulent after mutation of either glycoprotein J or virus host shutoff of herpes simplex virus type 1 wild-type. These recombinant viruses express the bacterial beta-galactosidase which is readily detectable using simple histochemistry. Inoculation of the adrenal gland or kidney with these viruses led to clear labelling of spinal cord cells. These viruses may be useful markers of specific neural circuits.