Tunicamycin inhibits glycosylation and multiplication of Sindbis and vesicular stomatitis viruses.
Tunicamycin (TM), an antibiotic that inhibits the formation of N-acetylglucosamine-lipid intermediates, thereby preventing the glycosylation of newly synthesized glycoproteins, inhibits the growth of Sindbis virus and vesicular stomatitis virus in BHK cells. At 0.5 mug of TM per ml, the replication of both viruses is inhibited 99.9%. Noninfectious particles were not detected. All the viral proteins were synthesized in the presence of TM, but the glycoproteins were selectively altered in that they migrated faster than normal viral glycoproteins when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting defective glycosylation. Within 1 h after TM addition, [14C]glucosamine incorporation into glycoproteins was inhibited 20%, whereas [35S]methionine incorporation was unaffected. By 2 to 3 h after TM addition, glucosamine incorporation had fallen to 15% of control value, with methionine incorporation being 60% of normal. TM did not affect the growth of the nomenveloped encephalomyocarditis virus in BHK cells, demonstrating that TM is not a general inhibitor of protein synthesis. These data demonstrate that TM specifically inhibits the glycosylation of viral glycoproteins and that glycosylation may be essential for the normal assembly of enveloped viral particles.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D004686:Encephalomyocarditis virus / Q000187:drug effects / Q000254:growth & development; D005944:Glucosamine / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis; D008715:Methionine / Q000378:metabolism; D012845:Sindbis Virus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
D000900:Anti-Bacterial Agents; D006023:Glycoproteins; D014764:Viral Proteins; D008715:Methionine; D005944:Glucosamine