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The antiviral role of zinc and metallothioneins in hepatitis C infection
Author(s) -
Read S. A.,
Parnell G.,
Booth D.,
Douglas M. W.,
George J.,
Ahlenstiel G.
Publication year - 2018
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12845
Subject(s) - metallothionein , zinc , gene knockdown , in vitro , in vivo , hepatitis c virus , biology , context (archaeology) , rna , oxidative stress , virology , intracellular , virus , chemistry , biochemistry , gene , paleontology , microbiology and biotechnology , organic chemistry
Summary Metallothioneins ( MT s) are small, cysteine‐rich proteins characterized by a high affinity for monovalent and divalent cations, such as copper and zinc. Of the four known MT isoforms, only, members of the MT 1 and 2 subfamilies are widely expressed, acting as metal chaperones whose primary role is to mediate intracellular zinc homoeostasis. Metallothioneins are potently induced by heavy metals and other sources of oxidative stress where they facilitate metal binding and detoxification as well as free radical scavenging. Metallothionein expression is well documented in the context of viral infection; however, it remains uncertain whether MTs possess specific antiviral roles or whether induction is merely a consequence of cellular stress. To better understand the role of MTs following hepatitis C virus ( HCV ) infection, we examined MT expression and localization in vitro and in vivo and used a si RNA knockdown approach to ascertain their antiviral efficacy. We confirmed HCV ‐driven MT induction in vitro and demonstrated MT accumulation in the nucleus of HCV ‐infected hepatocytes by immunofluorescence. Using a pan‐MT si RNA to knock down all members of the MT 1 and MT 2 subfamilies, we demonstrate that they are mildly antiviral against the JFH 1 strain of HCV in vitro (~1.4 fold increase in viral RNA , P < .05). Furthermore, the antiviral effect of zinc treatment against HCV in vitro was mediated through MT induction ( P < .05). Our data suggest a potential benefit of using zinc as a low‐cost adjunct to current HCV antiviral therapies and suggest that zinc may facilitate the antiviral role of MTs against other viruses.