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Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation
We have previously shown that physio/pathological levels of hydrogen peroxide (H(2)O(2)) stimulate translation from the hepatitis C virus (HCV) internal ribosome entry site (IRES) element in tissue-cultured cells. Here, using in vitro translation, we further show that H(2)O(2) upregulates HCV IRES-d...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Microbiology Society
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042130/ https://www.ncbi.nlm.nih.gov/pubmed/27436793 http://dx.doi.org/10.1099/jgv.0.000556 |
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author | Chan, Shiu-Wan |
author_facet | Chan, Shiu-Wan |
author_sort | Chan, Shiu-Wan |
collection | PubMed |
description | We have previously shown that physio/pathological levels of hydrogen peroxide (H(2)O(2)) stimulate translation from the hepatitis C virus (HCV) internal ribosome entry site (IRES) element in tissue-cultured cells. Here, using in vitro translation, we further show that H(2)O(2) 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 H(2)O(2) 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 H(2)O(2)-stimulated IRES-dependent translation is further confirmed by the ability of an anti-La antibody to suppress H(2)O(2)-activated IRES-dependent translation in vitro. This is further supported by the ability of an ectopically expressed dominant, negative La mutant protein to suppress H(2)O(2)-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 H(2)O(2), suggesting that H(2)O(2) 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. |
format | Online Article Text |
id | pubmed-5042130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Microbiology Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-50421302017-03-30 Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation Chan, Shiu-Wan J Gen Virol Standard We have previously shown that physio/pathological levels of hydrogen peroxide (H(2)O(2)) stimulate translation from the hepatitis C virus (HCV) internal ribosome entry site (IRES) element in tissue-cultured cells. Here, using in vitro translation, we further show that H(2)O(2) 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 H(2)O(2) 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 H(2)O(2)-stimulated IRES-dependent translation is further confirmed by the ability of an anti-La antibody to suppress H(2)O(2)-activated IRES-dependent translation in vitro. This is further supported by the ability of an ectopically expressed dominant, negative La mutant protein to suppress H(2)O(2)-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 H(2)O(2), suggesting that H(2)O(2) 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. Microbiology Society 2016-09 2016-09 /pmc/articles/PMC5042130/ /pubmed/27436793 http://dx.doi.org/10.1099/jgv.0.000556 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Standard Chan, Shiu-Wan Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation |
title | Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation |
title_full | Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation |
title_fullStr | Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation |
title_full_unstemmed | Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation |
title_short | Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation |
title_sort | hydrogen peroxide induces la cytoplasmic shuttling and increases hepatitis c virus internal ribosome entry site-dependent translation |
topic | Standard |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042130/ https://www.ncbi.nlm.nih.gov/pubmed/27436793 http://dx.doi.org/10.1099/jgv.0.000556 |
work_keys_str_mv | AT chanshiuwan hydrogenperoxideinduceslacytoplasmicshuttlingandincreaseshepatitiscvirusinternalribosomeentrysitedependenttranslation |