Herpes simplex virus infection of isolated autonomic neurons in culture: viral replication and spread in a neuronal network.

Cultures of isolated neurons, derived from the superior cervical ganglion (SCG) of the newborn rat and maintained in the absence of nonneuronal cells, were infected with herpes simplex virus (HSV) type 1. By phase-contrast microscopy, including time-lapse cinematography, cytopathologic changes appeared first in neuronal cell bodies and only approximately 24 hours later were axonal abnormalities detectable. Despite low yields of viral progeny, infection spread readily within the two-dimensional network of neurons and their processes. Immunoperoxidase staining for viral antigens confirmed the replication and spread of virus and revealed that antigen extended along axons during infection. Antiviral antibody added to the overlay medium slowed but did not prevent the spread of infection, indicating that virus passed from neuron to neuron over axonal pathways. Despite alteration of neuronal macromolecular synthesis early in infection, axonal transport is apparently preserved long enough to allow propagation of virus over interconnecting neural pathways.