engleski

Differential effects of ribonucleoside analogues on virus-directed RNA synthesis

Background and purpose: Two ribonucleoside analogues, 5-fluorouridine (FUrd) and 5-bromotubercidin (BrTu), were evaluated for their differential effects on virus-directed RNA synthesis and/or virus growth of six RNA viruses (mengo, sindbis, VSV, NDV, reo and influenza), and one DNA virus (vaccinia). Material and methods: Vaccinia, mengo, VSV and reovirus were grown in L2-cells; sindbis, NDV and influenza virus in chick embryo fibroblasts. The actinomycin insensitive RNA synthesis of mengovirus infected cells was measured in the presence of FUrd or BrTu. Results and conclusions: At a concentration (5mg/mll) sufficient irreversibly to block the synthesis of cellular rRNA , but not mRNA, FUrd reduced the growth of vaccinia virus only slightly. On the other hand, a low concentration of BrTu (5mg/ml) which blocks the synthesis of both cellular rRNA and mRNA reversibly, strongly reduced vaccinia virus growth. These data suggest that vaccinia-specific RNA synthesis is, like cellular mRNA synthesis, intrinsically unaffected by FUrd, but suppressed by BrTu. The multiplication of various RNA viruses gave a heterogenous group of responses to two analogues. The inhibition by BrTu on virus growth ranged from no effect or slight (mengo, sindbis, VSV, NDV), to strong effect (reo and influenza). Interestingly, BrTu was not incorporated into the viral RNA of mengovirus, which could be accounted for the virus growth resistance to the drug. The inhibitory effects of BrTu on reo and influenza viruses are probably exerted on viral and/or host cell functions connected with the multiplication cycles of these viruses. FUrd at concentrations (5-100 mg/ml) insufficient to block vaccinia-specific RNA synthesis, inhibited RNA-directed RNA synthesis and/or growth of mengo, VSV, NDV and influenza viruses strongly; sinbis and reovirus multiplications were adversely resistant to the drug. The virus specific target for antiviral action of FUrd against mengovirus is probably virus specific RNA synthesis, since the inhibitory antiviral effect required the constant presence of the analogue and thus, its incorporation into viral RNA.

virus-directed RNA synthesis; nucleoside analogues

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