Zinc is a negative regulator of hepatitis C virus RNA replication

Zinc is a negative regulator of hepatitis C virus RNA replication
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DOI:
10.1111/j.1478-3231.2006.01352.x
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发表时间:
2006-11-01
影响因子:
6.7
通讯作者:
Mori, Masatomo
Mori, Masatomo
中科院分区:
医学2区
文献类型:
--
作者:
Yuasa, Kazuhisa;Naganuma, Atsushi;Mori, Masatomo

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背景/目的:丙型肝炎病毒(HCV)感染是一个重要的全球性公共卫生问题。临床研究表明,锌与慢性丙型肝炎的发病密切相关。然而,锌在病毒复制和病毒蛋白表达中的作用仍不清楚。方法:用不同浓度的微量元素处理HCV亚基因组复制子细胞(sO)和基因组长度的HCV RNA复制细胞(O),观察锌对HCV复制的影响。结果:铁盐和α-干扰素抑制了sO和O细胞中HCV RNA的复制和蛋白的表达。锌盐有效地减少了病毒复制的基因组长度的HCV RNA复制系统,但不是在亚基因组HCV replicon system.Conclusions:我们表明,锌可能发挥重要作用,作为一个负调节基因组长度的HCV RNA复制细胞中的HCV复制。因此,锌补充似乎为治疗顽固性慢性丙型肝炎的未来策略的发展提供了一种新的方法。
Background/Aims: Hepatitis C virus (HCV) infection is a significant global public health problem. In clinical studies, zinc has been closely related to the pathogenesis of chronic hepatitis C. However, the role of zinc in both viral replication and the expression of viral proteins remains unclear. We aimed to clarify the effect of zinc on the replication of HCV in vitro.Method: We incubated subgenomic HCV replicon cells (sO) and genome-length HCV RNA-replicating cells (O) treated with several chemicals including trace elements. Total RNAs were collected and subjected to real-time reverse-transcriptase polymerase chain reaction in order to examine the level of HCV RNA replication, and Western blotting was performed to confirm the expression of viral proteins.Results: Iron salts and interferon-alpha suppressed HCV RNA replication and protein expression in both sO and O cells. Zinc salts effectively reduced the viral replication in the genome-length HCV RNA replication system but not in the subgenomic HCV replicon system.Conclusions: We demonstrated that zinc may play an important role as a negative regulator of HCV replication in genome-length HCV RNA-replicating cells. Zinc supplementation thus appears to offer a novel approach to the development of future strategies for the treatment of intractable chronic hepatitis C.