Stress-induced increase of hexose transport as a novel index of cytopathic effects in virus-infected cells: Role of the L protein in the action of vesicular stomatitis virus

Abstract

The VSV-specific increase in hexose transport by BHK cells has been measured by assay of the [ 3H]dGlc/[ 14C]AIB uptake ratio. The effect was abolished by uv-irradiation of the virus, indicating that viral gene expression is required. Cells infected with the T1026 R1 mutant of VSV, which causes only slight cytopathic changes, exhibited only a slight increase in hexose uptake. Cells infected with temperature-sensitive (ts) mutants of VSV that are defective in the function of the viral N, NS, G, or M proteins at the restrictive temperature (39.5°) exhibited increased [ 3H]dGLC/[ 14C]AIB uptake ratios typical of wild-type virus at either restrictive (39.5°) or permissive temperature (34°). Cells infected with a mutant defective in the function of the viral L protein exhibited an increased [ 3H]dGlc/[ 14C]AIB uptake ratio at permissive temperature (34°) only; at restrictive temperature (39.5°) the uptake ratio was essentially the same as that of mock-infected cells. Temperature-shift experiments indicated that the effect on hexose transport persisted for at least 6 hr in cells which no longer expressed function L protein, and that when expression of L was restricted to the first 2 hr of infection, an almost complete stimulation of hexose transport was observed 4 hr later. These results indicate that expression of the L gene is a necessary factor for inducing an increased hexose uptake in VSV-infected BHK cells. They also suggest that the action of the L protein on hexose transport is indirect, and is presumably mediated by other cellular constituents. The studies support the concept that an increased dGlc uptake may be a useful index of the cytopathic consequences of virus infection.