Abstract
One problem in divising strategies of gene transfer to the nevous system is targeting specific neuronal populations. To evaluate the potential for using herpes simplex virsu (HSV) as a vector for gene transfer to spinal cord motor neurons, the HSV-1 mutant LAT-LTR in which the E. coli β-galactrosidases gene is expressed under control of the HSV LAT core promoter (LAT) and the Moloney murine leukemia virus long terminal repeat (LTR) was inoculated unilaterally into the gastrocnemius muscle. Infections virus was isolated from the spinal cord on days 3-7 post inoculation (PI). Immunocytochemical labeling of HSV antigen was detected in ipsilateral ventral horn neurons in the spinal cord at day PI and had spread to contiguous spinal cord regions by day 6 PI. No viral antigen was detected to contiguous spinal cord regions by day 6 PI. No viral antigen was detected at 14 or 28 DPI. β-galactosidase expression (driven by the LAT-LTR promotor) was detected in neurons of the ventral horn on days 3, 6, 14, and 28 PI. Histological analysiss showed mild lesions in the ventral horn on day 3 PI which progressed through ways 6, 14 and 28 PI. This study demonstrates the feasibility of gene delivery into spinal motor neurons after injection of an HSV vector at a peripheral muscular site. This approach should prove useful in neurobiological investigations and it suggests a possible applications to development of gene therapy for heritable diseases affecting motor neurons.