Selective inhibition of avian sarcoma virus protein synthesis in 3-deazaadenosine-treated infected chicken embryo fibroblasts.

Abstract

The production of B77 avian sarcoma virions was inhibited more than 90% in infected chicken embryo fibroblasts that were treated with 100 microM 3-deazaadenosine, an inhibitor of adenosylhomocysteine hydrolase and, for this reason, an inhibitor of methylation reactions. This nucleoside analog at a concentration of 100 microM inhibited the rates of overall cellular protein synthesis and polyadenylated RNA synthesis by 40 to 50%. Rates of viral protein synthesis were compared, and the results indicated that in infected cells treated with 3-deazaadenosine syntheses of both the precursor of the gag proteins (pr76gag) and the precursor of the reverse transcriptase (pr180gag pol) were inhibited. Synthesis of the precursor of the viral envelope glycoproteins (pr92env) appeared to be affected less by the analog treatment. Most of the host polypeptides also continued to be synthesized in 3-deazaadenosine-treated cells. The fraction of the total RNA represented by virus-specific RNA in the 3-deazaadenosine-treated cells was approximately 40% of the fraction of the total RNA represented by viral RNA in control cells, as determined by hybridization kinetics. Therefore, there was a selective inhibition of viral RNA accumulation in the presence of 3-deazaadenosine. The amounts of genome-sized 35S and 38S RNAs were reduced compared with the amounts of 28S and 21S viral mRNA's. These results suggest that selective inhibition of the synthesis of viral proteins is due to selective decreases in the amounts of the mRNA's for these polypeptides.