SVLM21, a mutant of Sindbis virus able to grow in Aedes albopictus cells in the absence of methionine, shows increased sensitivity to S-adenosylhomocysteine hydrolase inhibitors such as neplanocin A.
Inhibition of S-adenosylhomocysteine (AdoHcy) hydrolase by compounds such as Neplanocin A (NPA) leads to the build-up of AdoHcy and the inhibition of methyltransferase enzymes. Whether assayed by efficiency of plaquing or virus yield, SVLM21, a mutant of Sindbis virus resistant to methionine deprivation, was more sensitive to NPA than was the standard virus (SVstd) from which it was derived. For example, whereas 10 micrograms NPA/ml depressed the yield of SVLM21 by more than 30-fold, the yield of SVstd was not significantly affected. Similar differences in sensitivities were shown to three other compounds which inhibit AdoHcy hydrolase. These results support the idea that SVLM21 codes for an altered RNA methyltransferase.
Durbin
R K
RK
Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635.
De Clercq
E
E
Stollar
V
V
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000330:Aedes; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D005814:Genes, Viral; D006867:Hydrolases / Q000037:antagonists & inhibitors; D008715:Methionine / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012436:S-Adenosylmethionine / Q000378:metabolism; D012845:Sindbis Virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology; D010948:Viral Plaque Assay
D000998:Antiviral Agents; C016391:9-(2,3-dihydroxypropyl)adenine; C031096:neplanocin A; D012436:S-Adenosylmethionine; C034072:carbocyclic 3-deazaadenosine; C048336:3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester; D008715:Methionine; D008780:Methyltransferases; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000225:Adenine; D000241:Adenosine; D014372:Tubercidin