Journal of Neuroscience, Vol 6, 391-402, Copyright © 1986 by Society for Neuroscience
Changes in excitability induced by herpes simplex viruses in rat dorsal root ganglion neurons
ML Mayer, MH James, RJ Russell, JS Kelly and CA Pasternak
The physiological properties of rat sensory neurons infected with herpes
simplex type 1 viruses and maintained in cell culture were studied using
intracellular recording techniques. Two syncytial (cell fusing) and two
nonsyncytial strains of virus were examined; individual strains of virus
had different effects on neuronal excitability. The nonsyncytial viruses
caused a loss of tetrodotoxin-sensitive low- threshold action potentials
and blocked hyperpolarization-activated inward rectification, but did not
alter the resting membrane potential, depolarization-activated outward
rectification, or render the cells leaky. These effects develop
progressively over the period 5-15 hr postinfection. One syncytial strain
of virus induced spontaneous electrical activity that appeared to be the
result of discrete electrical coupling between sensory neuron processes; as
a result, action potential discharge is synchronized in coupled neurons. A
second syncytial strain of virus rendered neurons inexcitable; however, in
these experiments the input resistance fell to low values, possibly as a
result of extensive coupling between sensory neurons. Viral replication in
sensory neurons was demonstrable with indirect immunofluorescence using an
antibody to herpes simplex viruses and correlated with the onset of virally
induced changes in excitability. Virally triggered changes in excitability
were blocked by the specific herpes virus antimetabolite acyclovir,
suggesting that viral adsorption and penetration are by themselves
insufficient to evoke changes in excitability. These results suggest that
herpes viruses have selective effects on the excitable mechanisms in
sensory neurons that are not simply the result of a general loss of
membrane conductances or the disruption of transmembrane ion gradients.