title: Comprehensive analysis of the effects of ordinary nutrients on hepatitis C virus RNA replication in cell culture.
abstract: 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-beta-carotene, vitamin D(2), 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, beta-carotene, vitamin D(2), 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.
authors.affiliation: Department of Molecular Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yano
authors.forename: Masanori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Abe
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Dansako
authors.forename: Shogo
authors.initials: S
authors.lastname: Ohkoshi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D045744:Cell Line, Tumor; D005227:Fatty Acids / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D018977:Micronutrients / Q000494:pharmacology*; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D012492:Salts / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D014815:Vitamins / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D005227:Fatty Acids; D018977:Micronutrients; D012367:RNA, Viral; D012492:Salts; D014815:Vitamins