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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Gen+Virol
2016 ; 97
(9
): 2301-2315
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Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C
virus internal ribosome entry site-dependent translation
#MMPMID27436793
Chan SW
J Gen Virol
2016[Sep]; 97
(9
): 2301-2315
PMID27436793
show ga
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.