Comprehensive analysis of the effects of ordinary nutrients on hepatitis C virus RNA replication in cell culture
Comprehensive analysis of the effects of ordinary nutrients on hepatitis C virus RNA replication in cell culture
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DOI：
10.1128/aac.01426-06
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发表时间：
2007-06-01
影响因子：
4.9
通讯作者：
Kato, Nobuyuki
中科院分区：
文献类型：
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作者：
Yano, Masahiko;Ikeda, Masanori;Kato, Nobuyuki
迄今为止，只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复制的影响。然而，其他营养素对HCV RNA复制的影响在很大程度上仍然未知。我们最近开发了一种报告基因检测系统，用于肝癌衍生的HuH-7细胞（OR 6）中基因组长度的HCV RNA复制。在这里，使用这种OR 6测定系统，我们全面检查了来自四个营养素组的46种营养素：维生素，氨基酸，脂肪酸和盐。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HCV RNA复制和它们的组合引起的叠加和/或协同作用对HCV RNA复制。此外，联合治疗与三种营养素和干扰素α或β或氟伐他汀抑制HCV RNA复制的累加方式，而联合治疗与环孢素协同抑制HCV RNA复制。相反，我们发现维生素E增强了HCV RNA的复制，并抵消了三种抗HCV营养素和环孢菌素的作用，但没有干扰素或氟伐他汀的作用。这些结果将为抗-HCV营养素联合干扰素治疗慢性丙型肝炎患者提供有用的信息。总之，在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。
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.