Rabies Virus Infection Selectively Impairs Membrane Receptor Functions in Neuronal Model Cells

Abstract

SUMMARYA persistent infection with rabies virus (HEP-Flury) was established in the CNS-derived hybrid cell line IO8 CC 15 which possesses specific membrane receptors for prostaglandins, catecholamines and acetylcholine. We report a differential virus influence on the specific receptor response to PGE, isoproterenol and acetycholine as indicated by typical changes of the intracellular cyclic AMP levels.As the adenylate cydase activity was unchanged in infected cells in vitro, a selective virus influence on specific receptors themselves or their coupling to the cAMP synthesizing system must be considered.

Neuronal Function Impairment in Rabies-infected Rat Brain

“…In our attempts to demonstrate a specific neuronal dysfunction after rabies infection we have shown that 3H-labelled QNB binding to mAChR varies during rabies infection in the rat brain. Our results contrast with observations that the response of rabies-infected 108-CC-15 cells to acetylcholine is unaffected, whereas the normal action of prostaglandin E1 and isoproterenol on the cAMP levels of these cells is impaired (Koschel & Halbach, 1979). Since in vitro studies mainly indicate the direct effect of rabies infection on cellular membrane modifications, further experiments will be carried out using N1E 115 neuroblastoma cells, which are also known to possess mAChR that binds 3H-labelled QNB (Burgermeister et al, 1978;Strange et al, 1978).…”

“…Whether the impairment of this specific neuronal function is due to the direct effect of rabies infection or through complex indirect mechanisms involving one or several steps is debatable. Other neuronal functions are certainly affected by rabies virus (Koschel & Halbach, 1979;Muenzel & Koschel, 1981) and it is known that mAChR also mediates inhibition of adenylate cyclase (Nathanson et al, 1978), and regulates cGMP and cAMP concentrations (Matsuzawa & Nirenberg, 1975). These and other regulatory mechanisms may play a role in rabies pathogenesis.…”

Virus-neuron interaction: an experimental model

“…But several viral infections of the brain also result in altered behavior, clinical expression of the disease and eventually death as in the case of rabies without a direct participation of cellular death. In these cases, the hypothesis that viruses can alter brain functions have been raised (Oldstone et al, 1977) and demonstrated for rabies virus infection (Koschel and Halbach, 1979;Tsiang, 1982). For such studies, it is compulsory to use neurobiological methods for the analysis and measure of altered functions.…”

Inhibition of rabies virus infection in cultured rat cortical neurons by an N-methyl-D-aspartate noncompetitive antagonist, MK-801

“…The virus-induced histopathological lesions are not a satisfactory explanation for the lethality of rabies virus (17), raising the possibility that virus-mediated neuronal dysfunction is involved. Previous studies examining the binding of radiolabeled antagonists to neurotransmitter receptors (11,12) and recording the electrical activity of chronically implanted mice (8) have shown that certain brain functions are modified during experimental rabies virus infection. Furthermore, early neuronal functional alterations can occur before the onset of clinical symptoms (8; also unpublished data).…”