Interference of nucleoside diphosphate derivatives of 2-deoxy-D-glucose with the glycosylation of virus-specific glycoproteins in vivo

Abstract

The predominant effect of 2-deoxy-D-glucose on chick embryo cells infected with Semliki Forest virus is an interference with glycosylation of virus-specific glycoproteins; this results in a block of synthesis of infectious virus. Incorporation of radioactive mannose is blocked severely in the presence of 2-deoxyglucose in the cultural medium although it is readily phosphorylated and subsequently activated by GTP to yield GDP-mannose, which accumulates under these conditions. The intracellular concentrations of GDP-mannose and UDP-N-acetyl-D-hexosamine are not reduced in the presence of the inhibitor. An equimolar concentration of mannose in the cultural medium competes with the inhibitory effect of the deoxysugar and drops the cellular pool of GDP-2-deoxy-D-glucose below the level of detection, at the same time restoring the synthesis of infectious virus. When the intracellular concentration of UDP-2-deoxyglucose is reduced by addition of glucose into the cultural medium the inhibition of virus synthesis by the deoxysugar and the concentration of GDP-2-deoxyglucose within the cells remain near to the values when the inhibitor is present alone. It is concluded that among the metabolites of 2-deoxyglucose which occur in vivo after addition of 2-deoxyglucose to the culture medium, GDP-2-deoxyglucose is the agent responsible for inhibition of glycosylation of viral glycoproteins.