Anesthetic action and virus replication: inhibition of measles virus replication in cells exposed to halothane

Abstract

Replication of measles virus in BSC cells was studied in the presence of halothane, a commonly used volatile anesthetic. At clinical concentrations of the anesthetic, appearance of progeny virus was decreased in a dose-related manner. This inhibition was reversible as the removal of halothane allowed virus replication to be resumed. Studies attempting to elucidate the mechanism of action of the anesthetic inhibition of virus replication revealed that halothane did not directly inactivate the virus particle or prevent viral adsorption to the cell. Infectious virus and nucleocapsid production were decreased or stopped, depending on the anesthetic dosage used. Direct immunofluorescent staining for measles virus antigen was negative in cells treated at the higher concentrations of halothane. Recovery of nucleocapsid production started within a few hours after removal of halothane. Furthermore, the combined inhibitory effects on viral ribonucleic acid synthesis of 5-azacytidine and halothane were additive. This evidence suggests that inhibition of measles virus replication occurs at or before ribonucleic acid synthesis.

Effect of halothane on the replication of animal viruses

“…Figure 1 demonstrates that MV replication was inhibited in a concentration-dependent manner when Vero cells were exposed to the anesthetic. The susceptibility of MV replication to halothane in Vero cells was similar to that previously described for BSC-1 cells (11). The susceptibility of MV replication to halothane in CV-1 cells is considerably greater, however, with total inhibition occurring at 1.2% (unpublished data).…”

“…Infected cultures were washed once with Tris-buffered saline (pH 7.4) after the adsorption period to remove nonadsorbed virus. Culture medium was then added, and the indicated concentration of halothane vapors was added immediately as described previously (11). When halothane-nonexposed, virus-infected Vero cell cultures demonstrated virus-specific cytopathology in 100% of the cells, they were harvested by quick freezing at -70°C along with cultures exposed to the concentrations of halothane indicated in the text.…”

“…Vesicular stomatitus virus (VSV) (Indiana strain), a gift of T. J. Schnitzer, was plaque purified five times through Vero cells. A dilute (11), with halothane concentrations being assessed by gas chromatography (11). Halothane was also removed from exposed cultures by changing the culture medium and passing a 95% air-5% CO2 airstream over the cultures as previously reported (11).…”

“…After two freeze-thaw cycles, the number of virus particles in the cell lysate was determined by the plaque assay technique as follows. Infectious MV, NDV, HSV, VSV, and poliovirus titers were measured by the plaque assay technique, using a methylcellulose overlay as previously described (11). Plaques were counted after 1 day for poliovirus, 2 days for VSV, 3 days for HSV, or 7 days for MV and NDV.…”

“…Exposure of measles virus (MV)-infected BSC-1 (monkey kidney) cells in culture to halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) results in a decrease in infectious progeny virus (11). Enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether) and its chemical isomer isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether) also inhibit MV replication in a concentration-dependent and reversible manner in BSC-1 cells (12).…”