Poliovirus and vesicular stomatitis virus replication in the presence of 6-diazo-5-oxo-L-norleucine or 2-deoxy-D-glucose.
The effects of 6-diazo-5-oxo-L-norleucine (DON), 2-deoxy-D-glucose (DOG), and tunicamycin (TM) on the replication of poliovirus (PV) and vesicular stomatitis virus (VSV) were examined. During a 48-hr replication period, TM, DON, and DOG inhibit VSV plaque formation in HEp-2 cells by 99.9%, 99.8%, and 99.9% respectively. Inhibition of VSV by DON is reversed with glutamine. Although all three agents are known to affect glycoprotein synthesis, DON and DOG also inhibit plaque formation of viruses devoid of structural glycoproteins. Thus, plaque formation of PV types 1 and 3 and Coxsackie B3 virus is delayed in HEp-2 and Buffalo green monkey kidney cells during exposure to these agents. Since these viruses do not contain glycoproteins and since concentrations up to 10 micrograms TM/ml cause no significant inhibition of PV, DON and DOG are affecting another viral or cellular process. Inhibition of PV replication by DON is reversed by addition of 25 mM glutamine or marginally by exposure to a combination of 5 mM concentrations of cytidine, uridine, adenosine monophosphate, and guanosine monophosphate. Inhibition of PV replication by DOG is reversed with 5 mM uridine alone. During DON exposure of HEp-2 cells infected with PV, the amount of 3H-uridine incorporation at 5.5 hr postinfection (pi) is reduced to 53% of untreated controls, an amount 11% greater than incorporation in cultures infected with PV but not treated with DON. These data indicate that the inhibition of PV replication by DON or DOG occurs at the level of viral RNA synthesis, while the primary target of these agents during VSV replication is probably glycosylation.
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003837:Deoxy Sugars / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D003980:Diazooxonorleucine / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009711:Nucleotides / Q000494:pharmacology; D017955:Poliovirus / Q000187:drug effects* / Q000502:physiology; D012313:RNA / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D014415:Tunicamycin / Q000494:pharmacology; D014529:Uridine / Q000378:metabolism / Q000494:pharmacology; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000502:physiology; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D001391:Azo Compounds; D003837:Deoxy Sugars; D009711:Nucleotides; D012367:RNA, Viral; D003980:Diazooxonorleucine; D005973:Glutamine; D014415:Tunicamycin; D012313:RNA; D003847:Deoxyglucose; D014529:Uridine