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Antimicrobial Agents and Chemotherapy, June 2007, p. 2016-2027, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01426-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Comprehensive Analysis of the Effects of Ordinary Nutrients on Hepatitis C Virus RNA Replication in Cell Culture{triangledown}

Masahiko Yano,1,2 Masanori Ikeda,1* Ken-ichi Abe,1 Hiromichi Dansako,1 Shogo Ohkoshi,2 Yutaka Aoyagi,2 and Nobuyuki Kato1

Department of Molecular Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558,1 Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata City, 951-8510, Japan2

Received 15 November 2006/ Returned for modification 1 February 2007/ Accepted 29 March 2007

To date, only a limited number of studies have reported finding an influence of ordinary nutrients on hepatitis C virus (HCV) RNA replication. However, the effects of other nutrients on HCV RNA replication remain largely unknown. We recently developed a reporter assay system for genome-length HCV RNA replication in hepatoma-derived HuH-7 cells (OR6). Here, using this OR6 assay system, we comprehensively examined 46 nutrients from four nutrient groups: vitamins, amino acids, fatty acids, and salts. We found that three nutrients—ß-carotene, vitamin D2, and linoleic acid—inhibited HCV RNA replication and that their combination caused additive and/or synergistic effects on HCV RNA replication. In addition, combined treatment with each of the three nutrients and interferon alpha or beta or fluvastatin inhibited HCV RNA replication in an additive manner, while combined treatment with cyclosporine synergistically inhibited HCV RNA replication. In contrast, we found that vitamin E enhanced HCV RNA replication and negated the effects of the three anti-HCV nutrients and cyclosporine but not those of interferon or fluvastatin. These results will provide useful information for the treatment of chronic hepatitis C patients who also take anti-HCV nutrients as an adjunctive therapy in combination with interferon. In conclusion, among the ordinary nutrients tested, ß-carotene, vitamin D2, and linoleic acid possessed anti-HCV activity in a cell culture system, and these nutrients are therefore considered to be potential candidates for enhancing the effects of interferon therapy.

* Corresponding author. Mailing address: Department of Molecular Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. Phone: 81-86-235-7386. Fax: 81-86-235-7392. E-mail: maikeda{at}md.okayama-u.ac.jp

{triangledown} Published ahead of print on 9 April 2007.

Antimicrobial Agents and Chemotherapy, June 2007, p. 2016-2027, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01426-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kuroki, M., Ariumi, Y., Ikeda, M., Dansako, H., Wakita, T., Kato, N. (2009). Arsenic Trioxide Inhibits Hepatitis C Virus RNA Replication through Modulation of the Glutathione Redox System and Oxidative Stress. J. Virol. 83: 2338-2348 [Abstract] [Full Text]  


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