Zinc is a negative regulator of hepatitis C virus RNA replication

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Zinc is a negative regulator of hepatitis C virus RNA replication

Authors: Yuasa, Kazuhisa1; Naganuma, Atsushi1; Sato, Ken1; Ikeda, Masanori2;

Kato, Nobuyuki2; Takagi, Hitoshi1; Mori, Masatomo1

Source: Liver International, Volume 26, Number 9, November 2006, pp.

1111-1118(8)

Publisher: Blackwell Publishing

Abstract:

Yuasa K, Naganuma A, Sato K, Ikeda M, Kato N, Takagi H, Mori M. Zinc is a

negative regulator of hepatitis C virus RNA replication.

Liver International 2006: 26: 1111-1118.

© 2006 The Authors. Journal compilation © 2006 Blackwell Munksgaard

Abstract: 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. Methods:

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-á 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.

Keywords: genome-length HCV RNA; hepatitis C virus; replication; subgenomic

HCV replicon; zinc

Document Type: Research article

DOI: 10.1111/j.1478-3231.2006.01352.x

Affiliations: 1: Department of Medicine and Molecular Science, Gunma

University Graduate School of Medicine, Gunma, Japan, 2: Department of

Molecular Biology, Okayama University Graduate School of Medicine,

Dentistry, and Pharmaceutical Sciences, Okayama, Japan

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