1887

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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000556
2016-09-01
2020-01-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/9/2301.html?itemId=/content/journal/jgv/10.1099/jgv.0.000556&mimeType=html&fmt=ahah

References

  1. Ayukawa K., Taniguchi S., Masumoto J., Hashimoto S., Sarvotham H., Hara A., Aoyama T., Sagara J.. 2000; La autoantigen is cleaved in the COOH terminus and loses the nuclear localization signal during apoptosis. J Biol Chem275:34465–34470 [CrossRef][PubMed]
    [Google Scholar]
  2. Bayfield M. A., Yang R., Maraia R. J.. 2010; Conserved and divergent features of the structure and function of La and La-related proteins (LARPs). Biochim Biophys Acta1799:365–378 [CrossRef][PubMed]
    [Google Scholar]
  3. Belsham G. J.. 2009; Divergent picornavirus IRES elements. Virus Res139:183–192 [CrossRef][PubMed]
    [Google Scholar]
  4. Blight K. J., Kolykhalov A. A., Rice C. M.. 2000; Efficient initiation of HCV RNA replication in cell culture. Science290:1972–1974 [CrossRef][PubMed]
    [Google Scholar]
  5. Boumlic A., Vassilaki N., Dalagiorgou G., Kochlios E., Kakkanas A., Georgopoulou U., Markoulatos P., Orfanoudakis G., Mavromara P.. 2011; Internal translation initiation stimulates expression of the ARF/core+1 open reading frame of HCV genotype 1b. Virus Res155:213–220 [CrossRef][PubMed]
    [Google Scholar]
  6. Brenet F., Socci N. D., Sonenberg N., Holland E. C.. 2009; Akt phosphorylation of La regulates specific mRNA translation in glial progenitors. Oncogene28:128–139 [CrossRef][PubMed]
    [Google Scholar]
  7. Chan S. W.. 2014; Establishment of chronic hepatitis C virus infection: translational evasion of oxidative defence. World J Gastroenterol20:2785–2800 [CrossRef][PubMed]
    [Google Scholar]
  8. Chan S. W., Egan P. A.. 2005; Hepatitis C virus envelope proteins regulate CHOP via induction of the unfolded protein response. FASEB J19:1510–1512 [CrossRef][PubMed]
    [Google Scholar]
  9. Chan S.-W., Egan P. A.. 2009; Effects of hepatitis C virus envelope glycoprotein unfolded protein response activation on translation and transcription. Arch Virol154:1631–1640 [CrossRef][PubMed]
    [Google Scholar]
  10. Choi J. N., Lee K. J., Zheng Y. Y., Yamaga A. K., Lai M. M., Ou J. H.. 2004; Reactive oxygen species suppress hepatitis C virus RNA replication in human hepatoma cells. Hepatology39:81–89 [CrossRef][PubMed]
    [Google Scholar]
  11. Collier A. J., Tang S. X., Elliott R. M.. 1998; Translation efficiencies of the 5′ untranslated region from representatives of the six major genotypes of hepatitis C virus using a novel bicistronic reporter assay system. J Gen Virol79:2359–2366 [CrossRef][PubMed]
    [Google Scholar]
  12. Costa-Mattioli M., Svitkin Y., Sonenberg N.. 2004; La autoantigen is necessary for optimal function of the poliovirus and hepatitis C virus internal ribosome entry site in vivo and in vitro. Mol Cell Biol24:6861–6870 [CrossRef][PubMed]
    [Google Scholar]
  13. Craig A. W., Svitkin Y. V., Lee H. S., Belsham G. J., Sonenberg N.. 1997; The La autoantigen contains a dimerization domain that is essential for enhancing translation. Mol Cell Biol17:163–169 [CrossRef][PubMed]
    [Google Scholar]
  14. Daba A., Koromilas A. E., Pantopoulos K.. 2012; Alternative ferritin mRNA translation via internal initiation. RNA18:547–556 [CrossRef][PubMed]
    [Google Scholar]
  15. Davies K. J. A.. 1999; The broad spectrum of responses to oxidants in proliferating cells: a new paradigm for oxidative stress. IUBMB Life48:41–47 [CrossRef][PubMed]
    [Google Scholar]
  16. Diamond D. L., Jacobs J. M., Paeper B., Proll S. C., Gritsenko M. A., Carithers R. L., Larson A. M., Yeh M. M., Camp D. G. et al. 2007; Proteomic profiling of human liver biopsies: hepatitis C virus-induced fibrosis and mitochondrial dysfunction. Hepatology46:649–657 [CrossRef][PubMed]
    [Google Scholar]
  17. Dickinson B. C., Chang C. J.. 2011; Chemistry and biology of reactive oxygen species in signaling or stress responses. Nat Chem Biol7:504–511 [CrossRef]
    [Google Scholar]
  18. Fujita N., Sugimoto R., Ma N., Tanaka H., Iwasa M., Kobayashi Y., Kawanishi S., Watanabe S., Kaito M., Takei Y.. 2008; Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C. J Viral Hepat15:498–507 [CrossRef][PubMed]
    [Google Scholar]
  19. Gendron K., Ferbeyre G., Heveker N., Brakier-Gingras L.. 2011; The activity of the HIV-1 IRES is stimulated by oxidative stress and controlled by a negative regulatory element. Nucleic Acids Res39:902–912 [CrossRef][PubMed]
    [Google Scholar]
  20. Giudetti A. M., Damiano F., Gnoni G. V., Siculella L.. 2013; Low level of hydrogen peroxide induces lipid synthesis in BRL-3A cells through a CAP-independent SREBP-1a activation. Int J Biochem Cell Biol45:1419–1426 [CrossRef][PubMed]
    [Google Scholar]
  21. Grant C. M.. 2011; Regulation of translation by hydrogen peroxide. Antioxid Redox Signal15:191–203 [CrossRef][PubMed]
    [Google Scholar]
  22. Hellen C. U. T., de Breyne S.. 2007; A distinct group of hepacivirus/pestivirus-like internal ribosomal entry sites in members of diverse picornavirus genera: evidence for modular exchange of functional noncoding RNA elements by recombination. J Virol81:5850–5863 [CrossRef][PubMed]
    [Google Scholar]
  23. Holcik M., Korneluk R. G.. 2000; Functional characterization of the X-Linked Inhibitor of apoptosis (XIAP) internal ribosome entry site element: role of la autoantigen in XIAP translation. Mol Cell Biol20:4648–4657 [CrossRef][PubMed]
    [Google Scholar]
  24. Huang M., Ida H., Arima K., Nakamura H., Aramaki T., Fujikawa K., Tamai M., Kamachi M., Kawakami A. et al. 2007; La autoantigen translocates to cytoplasm after cleavage during granzyme B-mediated cytotoxicity. Life Sci81:1461–1466 [CrossRef][PubMed]
    [Google Scholar]
  25. Intine R. V., Tenenbaum S. A., Sakulich A. L., Keene J. D., Maraia R. J.. 2003; Differential phosphorylation and subcellular localization of la RNPs associated with precursor tRNAs and translation-related mRNAs. Mol Cell12:1301–1307 [CrossRef][PubMed]
    [Google Scholar]
  26. Jack S. C., Chan S.-W.. 2011; The role of PERK and GCN2 in basal and hydrogen peroxide-regulated translation from the hepatitis C virus internal ribosome entry site. Virus Genes43:208–214 [CrossRef][PubMed]
    [Google Scholar]
  27. Jackson R. J.. 2005; Alternative mechanisms of initiating translation of mammalian mRNAs. Biochem Soc Trans33:1231–1241 [CrossRef][PubMed]
    [Google Scholar]
  28. Konishi M., Iwasa M., Araki J., Kobayashi Y., Katsuki A., Sumida Y., Nakagawa N., Kojima Y., Watanabe S. et al. 2006; Increased lipid peroxidation in patients with non-alcoholic fatty liver disease and chronic hepatitis C as measured by the plasma level of 8-isoprostane. J Gastroenterol Hepatol21:1821–1825 [CrossRef][PubMed]
    [Google Scholar]
  29. Kozak M.. 1987; An analysis of 5′-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res15:8125–8148 [CrossRef][PubMed]
    [Google Scholar]
  30. Kumar A., Ray U., Das S.. 2013; Human la protein interaction with GCAC near the initiator AUG enhances hepatitis C virus RNA replication by promoting linkage between 5′ and 3′ untranslated regions. J Virol87:6713–6726 [CrossRef][PubMed]
    [Google Scholar]
  31. Lewis S. M., Holcik M.. 2008; For IRES trans-acting factors, it is all about location. Oncogene27:1033–1035 [CrossRef]
    [Google Scholar]
  32. Li W., Thakor N., Xu E. Y., Huang Y., Chen C., Yu R., Holcik M., Kong A.-N.. 2010; An internal ribosomal entry site mediates redox- sensitive translation of Nrf2. Nucleic Acids Res38:778–788 [CrossRef][PubMed]
    [Google Scholar]
  33. MacCallum P. R., Jack S. C., Egan P. A., McDermott B. T., Elliott R. M., Chan S.-W.. 2006; Cap-dependent and hepatitis C virus internal ribosome entry site-mediated translation are modulated by phosphorylation of eIF2 under oxidative stress. J Gen Virol87:3251–3262 [CrossRef][PubMed]
    [Google Scholar]
  34. McCartney E. M., Semendric L., Helbig K. J., Hinze S., Jones B., Weinman S. A., Beard M. R.. 2008; Alcohol metabolism increases the replication of hepatitis C virus and attenuates the antiviral action of interferon. J Infect Dis198:1766–1775 [CrossRef][PubMed]
    [Google Scholar]
  35. Paracha U. Z., Fatima K., Alqahtani M., Chaudhary A., Abuzenadah A., Damanhouri G., Qadri I.. 2013; Oxidative stress and hepatitis C virus. Virol J10:251 [CrossRef][PubMed]
    [Google Scholar]
  36. Paradis V., Kollinger M., Fabre M., Holstege A., Poynard T., Bedossa P.. 1997; In situ detection of lipid peroxidation by-products in chronic liver diseases. Hepatology26:135–142 [CrossRef]
    [Google Scholar]
  37. Petz M., Them N., Huber H., Beug H., Mikulits W.. 2012; La enhances IRES-mediated translation of laminin B1 during malignant epithelial to mesenchymal transition. Nucleic Acids Res40:290–302 [CrossRef]
    [Google Scholar]
  38. Plank T.-D., Kieft J. S.. 2012; The structures of nonprotein-coding RNAs that drive internal ribosome entry site function. Wiley Interdiscip Rev RNA3:195–212 [CrossRef][PubMed]
    [Google Scholar]
  39. Pudi R., Srinivasan P., Das S.. 2004; La protein binding at the GCAC site near the initiator AUG facilitates the ribosomal assembly on the hepatitis C virus RNA to influence internal ribosome entry site-mediated translation. J Biol Chem279:29879–29888 [CrossRef][PubMed]
    [Google Scholar]
  40. Romero V., Fellows E., Jenne D. E., Andrade F.. 2009; Cleavage of La protein by granzyme H induces cytoplasmic translocation and interferes with La-mediated HCV-IRES translational activity. Cell Death Differ16:340–348 [CrossRef][PubMed]
    [Google Scholar]
  41. Rutjes S. A., Utz P. J., van der Heijden A., Broekhuis C., van Venrooij W. J., Pruijn G. J.. 1999; The La (SS-B) autoantigen, a key protein in RNA biogenesis, is dephosphorylated and cleaved early during apoptosis. Cell Death Differ6:976–986 [CrossRef][PubMed]
    [Google Scholar]
  42. Sella O., Gerlitz G., Le S. Y., Elroy-Stein O.. 1999; Differentiation-induced internal translation of c-sis mRNA: analysis of the cis elements and their differentiation-linked binding to the hnRNP C protein. Mol Cell Biol19:5429–5440 [CrossRef][PubMed]
    [Google Scholar]
  43. Shiroki K., Isoyama T., Kuge S., Ishii T., Ohmi S., Hata S., Suzuki K., Takasaki Y., Nomoto A.. 1999; Intracellular redistribution of truncated La protein produced by poliovirus 3C(pro)-mediated cleavage. J Virol73:2193–2200[PubMed]
    [Google Scholar]
  44. Stehbens W. E.. 2004; Oxidative stress in viral hepatitis and AIDS. Exp Mol Pathol77:121–132 [CrossRef][PubMed]
    [Google Scholar]
  45. Sweeney T. R., Dhote V., Yu Y., Hellen C. U.. 2012; A distinct class of internal ribosomal entry site in members of the Kobuvirus and proposed Salivirus and Paraturdivirus genera of the Picornaviridae. J Virol86:1468–1486 [CrossRef][PubMed]
    [Google Scholar]
  46. Tsukiyama-Kohara K., Iizuka N., Kohara M., Nomoto A.. 1992; Internal ribosome entry site within hepatitis C virus RNA. J Virol66:1476–1483[PubMed]
    [Google Scholar]
  47. Veal E. A., Day A. M., Morgan B. A.. 2007; Hydrogen peroxide sensing and signaling. Mol Cell26:1–14 [CrossRef][PubMed]
    [Google Scholar]
  48. Venturini D., Simão A. N., Barbosa D. S., Lavado E. L., Narciso V. E., Dichi I., Dichi J. B, Colado Simao A. N.. 2010; Increased oxidative stress, decreased total antioxidant capacity, and iron overload in untreated patients with chronic hepatitis c. Dig Dis Sci55:1120–1127 [CrossRef][PubMed]
    [Google Scholar]
  49. Wolin S. L., Cedervall T.. 2002; The La protein. Annu Rev Biochem71:375–403 [CrossRef][PubMed]
    [Google Scholar]
  50. Yamashita T., Kaneko S., Hashimoto S., Sato T., Nagai S., Toyoda N., Suzuki T., Kobayashi K., Matsushima K.. 2001; Serial analysis of gene expression in chronic hepatitis c and hepatocellular carcinoma. Biochem Biophys Res Commun282:647–654 [CrossRef][PubMed]
    [Google Scholar]
  51. Yeh S. H., Yang W. B., Gean P. W., Hsu C. Y., Tseng J. T., Su T. P., Chang W. C., Hung J. J.. 2011; Translational and transcriptional control of Sp1 against ischaemia through a hydrogen peroxide-activated internal ribosomal entry site pathway. Nucleic Acids Res39:5412–5423 [CrossRef][PubMed]
    [Google Scholar]
  52. Zhang W., Wang X., Xiao Z., Liu W., Chen B., Dai J.. 2010; Mapping of the minimal internal ribosome entry site element in the human embryonic stem cell gene OCT4B mRNA. Biochem Biophys Res Commun394:750–754 [CrossRef][PubMed]
    [Google Scholar]
  53. Zhang J., Thai Nho D., Kappeler K., Tsaprailis G., Chen Q. M.. 2012; La autoantigen mediates oxidant induced de novo Nrf2 protein translation. Mol Cell Proteomics11:015032 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000556
Loading
/content/journal/jgv/10.1099/jgv.0.000556
Loading

Data & Media loading...

Most cited articles

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error