Changes in excitability induced by herpes simplex viruses in rat dorsal root ganglion neurons

Abstract

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.

Mumps Virus-induced Alterations in Cellular Excitability During Persistent Infections

“…However, they contrast with other studies of acute herpes virus infections which show an increased excitability as reflected by the appearance of spontaneous electrical activity in infected cells (Kiraly & Dolivo, 1982;Mayer et al, 1985Mayer et al, , 1986. These opposite effects are probably the result of different virus-specific proteins interacting in various ways with the host cells.…”

“…This type of alteration has been demonstrated in acute, and in reactivating latent herpesvirus infections (Fukuda & Kurata 1981 ;Oakes et al, 1981 ;Kiraly & Dolivo, 1982;Fukuda et al, 1983 ;Mayer • . et al, 1985Mayer • . et al, , 1986), but has not been identified as a component of persistent virus pathogenesis.…”

Cellular gene expression survey of PseudoRabies Virus (PRV) infected Human Embryonic Kidney cells (HEK-293)

“…Modifications of the electrophysiological properties of membranes have been described in HSV-1 infected neurons [15,24,25,35] and the involvement of ion channels demonstrated in the spontaneous bursting activity observed in the superior cervical ganglion of PRV-infected rats [22]. Our results indicate that the potassium transport process was significantly up-regulated (23 genes up-regulated, z score = 3.37) compared to sodium transport, which does not appear in our list of gene ontology terms (Tab.…”

Selective block of inward but not outward rectification in rat sensory neurones infected with herpes simplex virus.

“…Such studies are complicated by the occurrence of multiple strains of herpes simplex viruses, including those with cell fusing properties (syncitial strains). The syncitial and non-syncitial strains appear to have differing effects on membrane physiology (Mayer, James, Russell, Kelly & Pasternak, 1986), and in a previous series of experiments designed to study possible changes in sensory neurone physiology following infection with herpes simplex type 1 viruses it was noted that the time-dependent sag distorting hyperpolarizing electrotonic potentials, and characteristic of inward rectification (Ito, 1957;Mayer & Westbrook, 1983), was absent following infection with non-syncitial strains of virus (Mayer, James, Russell, Kelly & Pasternak, 1986). The present series of voltage-clamp experiments were performed to study in greater detail the effects of herpes simplex virus infection on membrane rectification in sensory neurones.…”