1887

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Volume 97, Issue 9

Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation Open Access

Abstract

We have previously shown that physio/pathological levels of hydrogen peroxide (HO) stimulate translation from the hepatitis C virus (HCV) internal ribosome entry site (IRES) element in tissue-cultured cells. Here, using translation, we further show that HO upregulates HCV IRES-dependent mRNA translation and correlates with an increase in intracellular oxidant level. Using Western blotting, immunocytochemistry, microscopy and affinity pulldown, we show that HO stimulates HCV IRES-dependent translation and correlates with nuclear–cytoplasmic shuttling of the La autoantigen, resulting in enhanced binding of cytoplasmic La to HCV IRES RNA. The role of the La protein in HO-stimulated IRES-dependent translation is further confirmed by the ability of an anti-La antibody to suppress HO-activated IRES-dependent translation . This is further supported by the ability of an ectopically expressed dominant, negative La mutant protein to suppress HO-inducible IRES-mediated translation in Huh7 cells, transiently transfected with a bicistronic reporter and in a sub-genomic replicon cell line resembling a persistent infection. On the other hand, translation from the encephalomyocarditis virus IRES is diminished in the presence of HO, suggesting that HO translational responsiveness is a specific property of the HCV IRES and is not a general phenomenon for all viral IRESs. Altogether, these results suggest that HCV adapts to physio/pathological oxidative stress in the host cell by mediating La cytoplasmic shuttling to enhance its IRES-dependent translation.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): hepatitis C virus , hydrogen peroxide , IRES , La , oxidative stress and translation
© 2016 The Authors
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2016-09-01
2024-04-25
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Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation
J. Gen. Virol. 97, 2301 (2016); https://doi.org/10.1099/jgv.0.000556
/content/journal/jgv/10.1099/jgv.0.000556
/content/journal/jgv/10.1099/jgv.0.000556
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