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Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation
- Source :
- Chan, S-W 2016, ' Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation ', The Journal of general virology, vol. 97, pp. 2301–2315 . https://doi.org/10.1099/jgv.0.000556, The Journal of General Virology
- Publication Year :
- 2016
-
Abstract
- We have previously shown that physio/pathological levels of hydrogen peroxide (H2O2) 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 H2O2 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 H2O2 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 H2O2-stimulated IRES-dependent translation is further confirmed by the ability of an anti-La antibody to suppress H2O2-activated IRES-dependent translation in vitro. This is further supported by the ability of an ectopically expressed dominant, negative La mutant protein to suppress H2O2-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 H2O2, suggesting that H2O2 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.
- Subjects :
- 0301 basic medicine
hepatitis C virus
translation
hydrogen peroxide
Hepacivirus
Biology
Internal Ribosome Entry Sites
Virus Replication
Virus
Cell Line
Hepatitis C virus internal ribosome entry site
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Mutant protein
IRES
Virology
Protein biosynthesis
Humans
oxidative stress
Encephalomyocarditis virus
La
Animal
fungi
RNA
Translation (biology)
Transfection
Oxidants
Phosphoproteins
Molecular biology
Standard
Internal ribosome entry site
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Protein Biosynthesis
Hepatocytes
RNA, Viral
Positive-strand RNA Viruses
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Chan, S-W 2016, ' Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation ', The Journal of general virology, vol. 97, pp. 2301–2315 . https://doi.org/10.1099/jgv.0.000556, The Journal of General Virology
- Accession number :
- edsair.doi.dedup.....1f7bc132f9fc10e001da7b04e1785f36