Zinc is a negative regulator of hepatitis C virus RNA replication.
OBJECTIVE
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-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.
Yuasa
Kazuhisa
K
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Naganuma
Atsushi
A
Sato
Ken
K
Ikeda
Masanori
M
Kato
Nobuyuki
N
Takagi
Hitoshi
H
Mori
Masatomo
M
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016679:Genome, Viral; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D058085:Iron Compounds / Q000494:pharmacology; D049410:Luciferases, Renilla / Q000037:antagonists & inhibitors; D012367:RNA, Viral / Q000037:antagonists & inhibitors*; D012093:Replicon / Q000187:drug effects; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects*; D017967:Zinc Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D003603:Cytotoxins; D016898:Interferon-alpha; D058085:Iron Compounds; D049410:Luciferases, Renilla; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D017967:Zinc Compounds; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase