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Studies of Rous sarcoma virus. Effects of nucleoside analogues on virus synthesis.

Abstract We have studied the effects of two nucleoside analogues on the synthesis of Rous sarcoma virus and cellular RNA in monolayer cultures of chick embryo fibroblasts. The analogues are 5-fluorouridine and 5-bromotubercidin. 5-Fluorouridine irreversibly inhibits the synthesis of cellular RNA by more than 80%. Most of this inhibition is due to an irreversible block in the formation of ribosomal RNA. Protein synthesis continues at disproportionately elevated rates for several days, suggesting that messenger RNA synthesis also is maintained. The synthesis of heterogeneous nuclear RNA is not blocked by 5-fluorouridine; the same holds for the Rous sarcoma virus-RNA and Rous sarcoma virus-protein. Although normal quantities of Rous sarcoma virus are produced in cultures exposed to 5-fluorouridine, the infectivity is decreased; this is correlated with a profound inhibition of viral glycoprotein synthesis, and is in contrast to the effect of the aglycone, 5-fluorouracil, which does not decrease infectious virus yield under the same conditions. In contrast to the effects of 5-fluorouridine, 5-bromotubercidin reversibly blocks the synthesis of heterogeneous nuclear RNA as well as that of ribosomal RNA. Likewise 5-bromotubercidin blocks the synthesis of Rous sarcoma virus-RNA and, following a lag period of 8 to 10 hours, 5-bromotubercidin also inhibits the synthesis of viral proteins and mature virions. In relation to the action of the analogues, the synthesis of Rous sarcoma virus-RNA shares the specificity of heterogeneous RNA and mRNA.