Author: Lee, Kyungjin; Kim, Dong-Eun; Jang, Kyoung-Soon; Kim, Seong-Jun; Cho, Sungchan; Kim, Chonsaeng
Title: Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion Cord-id: jv76j6wx Document date: 2017_12_15
ID: jv76j6wx
Snippet: Gemcitabine, an anti-cancer chemotherapy drug, has additionally shown the antiviral activity against a broad range of viruses and we also have previously reported its synergistic antiviral activity with ribavirin against enteroviruses. As a cytidine analog, gemcitabine has been reported to have an inhibitory activity on the pyrimidine biosynthesis. In addition, a few inhibitors of the pyrimidine biosynthesis have shown to induce the innate immunity in a yet-to-be-determined manner and inhibit th
Document: Gemcitabine, an anti-cancer chemotherapy drug, has additionally shown the antiviral activity against a broad range of viruses and we also have previously reported its synergistic antiviral activity with ribavirin against enteroviruses. As a cytidine analog, gemcitabine has been reported to have an inhibitory activity on the pyrimidine biosynthesis. In addition, a few inhibitors of the pyrimidine biosynthesis have shown to induce the innate immunity in a yet-to-be-determined manner and inhibit the virus infection. Thus, we also investigated whether the anti-enteroviral activity of gemcitabine is mediated by innate immunity, induction of which is related with the inhibition of the pyrimidine synthesis. In this study, we found that the addition of exogenous cytidine, uridine and uridine mono-phosphate (UMP) effectively reversed the antiviral activity of gemcitabine in enterovirus-infected as well as enteroviral replicon-harboring cells, demonstrating gemcitabine’s targeting of the salvage pathway. Moreover, the expression of several interferon (IFN)-stimulated genes (ISGs) was significantly induced by the treatment of gemcitabine, which was also suppressed by the co-treatment with cytidine. These results suggest that the antiviral activity of gemcitabine involves ISGs induced by the inhibition of the pyrimidine biosynthesis.
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