Yano Masahiko, Ikeda Masanori, Abe Ken-Ichi, Dansako Hiromichi, Ohkoshi Shogo, Aoyagi Yutaka, Kato Nobuyuki
Department of Molecular Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Antimicrob Agents Chemother. 2007 Jun;51(6):2016-27. doi: 10.1128/AAC.01426-06. Epub 2007 Apr 9.
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.
迄今为止，仅有有限数量的研究报告发现普通营养素对丙型肝炎病毒（HCV）RNA复制有影响。然而，其他营养素对HCV RNA复制的影响仍 largely未知。我们最近开发了一种用于在肝癌来源的HuH-7细胞（OR6）中进行全长HCV RNA复制的报告基因检测系统。在此，使用该OR6检测系统，我们全面检测了来自四个营养组的46种营养素：维生素、氨基酸、脂肪酸和盐类。我们发现三种营养素——β-胡萝卜素、维生素D（2）和亚油酸——抑制了HCV RNA复制，并且它们的组合对HCV RNA复制产生了相加和/或协同作用。此外，三种营养素中的每一种与干扰素α或β或氟伐他汀联合治疗以相加方式抑制HCV RNA复制，而与环孢素联合治疗则协同抑制HCV RNA复制。相比之下，我们发现维生素E增强了HCV RNA复制，并抵消了三种抗HCV营养素和环孢素的作用，但没有抵消干扰素或氟伐他汀的作用。这些结果将为慢性丙型肝炎患者的治疗提供有用信息，这些患者也将抗HCV营养素作为与干扰素联合的辅助治疗。总之，在所测试的普通营养素中，β-胡萝卜素、维生素D（2）和亚油酸在细胞培养系统中具有抗HCV活性，因此这些营养素被认为是增强干扰素治疗效果的潜在候选物。
