Histological study of the progression of herpes simplex virus in mice

The progress of an experimental infection with Herpesvirus hominis type 1 was studied in newborn mice inoculated into the foot pad of the hind leg. To trace the viral antigen, the unlabeled antibody enzyme PAP (peroxidase/antiperoxidase) method was employed. The virus antigen appeared first in the epidermal and connective tissue cells of the inoculation site, and then progressed along the sciatic nerve. This nerve was studied by electron microscopy and showed active multiplication within the Schwann cells, with the production of virions, some of which were found in the intercellular spaces. No intra-axonal particles were observed. The infection then spread to the spinal ganglia and to the spinal cord. In this progression, the pia mater appeared to play an important role. From the spinal cord, the infection spread to the encephalon. The present study supports a mixed route for the neural transport of herpes simplex virus: a) by cell-to-cell transmission (Schwann and connective tissue cells in the sciatic nerve; meningeal cells, neurons and glial cells in the CNS); b) by a passive motion of the virions along the intercellular spaces. The inoculated virus also gave rise to viremia with viral multiplication in several viscera.