Inhibition of the Multiplication of Enveloped RNA-viruses by Glucosamine and 2-Deoxy-D-Glucose

Abstract

SUMMARYGlucosamine inhibited the formation of infectious fowl plague, Sindbis, and Semliki Forest virus but had little or no effect on the multiplication of vesicular stomatitis, Newcastle disease, and polio virus. 2-deoxy-o-glucose had a somewhat stronger effect than glucosamine. Only the production of virus glycoproteins seemed to be affected. Almost normal amounts of virus RNA and RNA polymerase were synthesized, and RNP-antigen activities reached control levels. After infection with fowl plague virus the nuclei and cytoplasm of cells incubated with glucosamine showed brilliant staining with fluorescent antibodies against RNP-antigen, whereas haemagglutinin-specific fluorescence was visible weakly in the cytoplasm. The virus-induced alterations of the cell surface, as measured by the agglutinability with Concanavalin A, were abolished by glucosamine.

WHOLE-BODY AUTORADIOGRAPHY OF DISTRIBUTION OF [1-¹⁴C]-2-DEOXYGLUCOSE IN MICE

“…It is generally accepted that 2-deoxyglucose is not metabolized beyond deoxyglucose-6-phosphate (7,8,9,12,14,17,18). However, in their studies with yeast, Biely and Bauer indicated that 2-deoxyglucose could be converted into uridine diphosphate-2-deoxyglucose (2) and guanosine diphosphate-deoxyglucose (4).…”

“…2-Deoxy-D-glucose (2-deoxyglucose), analogous to D-glucose, has been extensively used for the study of sugar transport and utilization in several tissues (5,6,7,10,13,15,16,20,26), because the carrier which transports 2-deoxyglucose into animal cells is the same for D-glucose, and its metabolism in the cytoplasm does not proceed beyond phosphorylation by hexokinase (8,9,12,14,17,18). Recently, however, there are some suggestions that 2-deoxyglucose might be metabolized further and incorporated into lipids (1,2,4,11,21,22,23,24).…”

Assembly of lipid‐containing viruses

“…High con- centrations of glucosamine have a similar inhibitory effect, and in the presence of these inhibitors the synthesis of the hemagglutinin polypeptide is not detected (44)(45)(46). Instead, a different polypeptide component designated HAo which migrates more rapidly than the HA polypeptide is produced in inhibitor-treated cells, and it appears that this is an unglycosylated or incompletely glycosylated precursor of the HA polypeptide (46,47).…”

“…Two different approaches have been used to modify the carbohydrate composition. First, we have employed inhibitors of glycosylation (44,45) which result in the production of aberrant glycoproteins of higher electrophoretic mobility, which are not labeled by carbohydrate precursors (46). In the presence of such inhbitors, virus particles containing the aberrant While the available data suggest that glycosylated and nonglycosylated envelope glycoproteins are produced, and their infectivity and hemagglutinating activity is markedly lower.…”

Carbohydrate distribution in mammal; Whole-body autoradiographic approach.

“…12), and its metabolism in the cytoplasm does not proceed beyond phosphorylation by hexokinase (17,19,21,33,35). Autoradiography off radioactive 2-deoxyglucose has been used to measure the glucose utilization in different brain regions by Reivich (31) and Sokoloff (46).…”