Hydroxyurea as an inhibitor of hepatitis C virus RNA replication
- 103 Downloads
Hepatitis C virus (HCV) is the main causative agent of chronic liver disease, which may develop into liver cirrhosis and hepatocellular carcinoma. By using a recently developed reporter assay system in which genome-length HCV RNA replicates efficiently, we found that hydroxyurea (HU), a DNA synthesis inhibitor, inhibited HCV RNA replication. Moreover, we demonstrated that the anti-HCV activity of the combination of IFN-alpha and HU was higher than that of IFN-alpha alone. These results suggest that HU may be an effective anti-HCV reagent that can be used not only singly but also in combination with IFN-alpha to treat chronic hepatitis C.
KeywordsInternal Ribosome Entry Site Human Immunodeficiency Virus Inhibition
The authors thank Kazue Yoshihara and Yoshiko Kubushiro for their technical assistance. This work was supported by a grant for the 2008 Strategic Research Project (No. W20012) provided by Yokohama City University, Japan.
- 12.Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE, Tegtmeier GE, Bonino F, Colombo WS, Lee WS, Kuo C, Berger K, Shuster JR, Overby LR, Bradley DW, Houghton M (1989) An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244:362–364CrossRefPubMedGoogle Scholar
- 14.Lori F, Jessen H, Lieberman J, Finzi D, Rosenberg E, Tinelli C, Walker B, Siliciano RF, Lisziewicz J (1999) Treatment of human immunodeficiency virus infection with hydroxyurea, didanosine, and a protease inhibitor before seroconversion is associated with normalized immune parameters and limited viral reservoir. J Infect Dis 180:1827–1832CrossRefPubMedGoogle Scholar
- 15.Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358:958–965CrossRefPubMedGoogle Scholar
- 22.Tanabe Y, Sakamoto N, Enomoto N, Kurosaki M, Ueda E, Maekawa S, Yamashiro T, Nakagawa M, Chen CH, Kanazawa N, Kakinuma S, Watanabe M (2004) Synergistic inhibition of intracellular hepatitis C virus replication by combination of ribavirin and interferon-alpha. J Infect Dis 189:1129–1139CrossRefPubMedGoogle Scholar
- 23.The Benelux CML, Group Study (1998) Randomized study on hydroxyurea alone versus hydroxyurea combined with low-dose interferon-alpha 2b for chronic myeloid leukemia. Blood 91:2713–2721Google Scholar