Hepatitis C Virus Down-Regulates the Expression of Ribonucleotide Reductases to Promote Its Replication

Ribonucleotide reductases (RRs or RNRs) catalyze the reduction of OH group on 2nd carbon ribose, reducing four ribonucleotides (NTPs) to corresponding deoxyribonucleotides (dNTPs) promote DNA synthesis. Large viruses, such as herpesviruses and poxviruses, could benefit their replication through increasing dNTPs via expression viral RRs. Little is known regarding relationship between cellular RRs RNA viruses. Mammalian contain two subunits ribonucleotide reductase M1 polypeptide (RRM1) M2 (RRM2). In this study, RRMs, including RRM1 RRM2, found be down-regulated in hepatitis C virus (HCV)-infected Huh7.5 cells Huh7 with HCV subgenomic RNAs (HCVr). As expected, NTP/dNTP ratio elevated HCVr cells. Compared that control sh-scramble, RRM-knockdown elevated. Knockdown RRM2 increases replicon Moreover, inhibitors Didox, Trimidox hydroxyurea, enhance replication. Among various proteins, NS5A and/or NS3/4A proteins suppress RRMs. When these are taken together, results suggest down-regulates RRMs cultured its