1887

Abstract

Staufen1 is a dsRNA-binding protein involved in the regulation of translation and the trafficking and degradation of cellular RNAs. Staufen1 has also been shown to stimulate translation of human immunodeficiency virus type 1 (HIV-1) RNA, regulate HIV-1 and influenza A virus assembly, and there is also indication that it can interact with hepatitis C virus (HCV) RNA. To investigate the role of Staufen1 in the HCV replication cycle, the effects of small interfering RNA knockout of Staufen1 on HCV strain JFH-1 replication and the intracellular distribution of the Staufen1 protein during HCV infection were examined. Silencing Staufen1 in HCV-infected Huh7 cells reduced virus secretion by around 70 %, intracellular HCV RNA levels by around 40 %, and core and NS3 proteins by around 95 and 45 %, respectively. Staufen1 appeared to be predominantly localized in the endoplasmic reticulum at the nuclear periphery in both uninfected and HCV-infected Huh7 cells. However, Staufen1 showed significant co-localization with NS3 and dsRNA, indicating that it may bind to replicating HCV RNA that is associated with the non-structural proteins. Staufen1 and HCV core protein localized very closely to one another during infection, but did not appear to overlap, indicating that Staufen1 may not bind to core protein or localize to the core-coated lipid droplets, suggesting that it may not be directly involved in HCV virus assembly. These findings indicate that Staufen1 is an important factor in HCV replication and that it might play a role early in the HCV replication cycle, e.g. in translation, replication or trafficking of the HCV genome, rather than in virion morphogenesis.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.051383-0
2013-11-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/94/11/2429.html?itemId=/content/journal/jgv/10.1099/vir.0.051383-0&mimeType=html&fmt=ahah

References

  1. Abrahamyan L. G., Chatel-Chaix L., Ajamian L., Milev M. P., Monette A., Clément J. F., Song R., Lehmann M., DesGroseillers L.other authors 2010; Novel Staufen1 ribonucleoproteins prevent formation of stress granules but favour encapsidation of HIV-1 genomic RNA. J Cell Sci 123:369–383 [View Article][PubMed]
    [Google Scholar]
  2. Belov G. A., Habbersett C., Franco D., Ehrenfeld E. 2007; Activation of cellular Arf GTPases by poliovirus protein 3CD correlates with virus replication. J Virol 81:9259–9267 [View Article][PubMed]
    [Google Scholar]
  3. Blackham S., Baillie A., Al-Hababi F., Remlinger K., You S., Hamatake R., McGarvey M. J. 2010; Gene expression profiling indicates the roles of host oxidative stress, apoptosis, lipid metabolism, and intracellular transport genes in the replication of hepatitis C virus. J Virol 84:5404–5414 [View Article][PubMed]
    [Google Scholar]
  4. Bruce E. A., Digard P., Stuart A. D. 2010; The Rab11 pathway is required for influenza A virus budding and filament formation. J Virol 84:5848–5859 [View Article][PubMed]
    [Google Scholar]
  5. Coller K. E., Berger K. L., Heaton N. S., Cooper J. D., Yoon R., Randall G. 2009; RNA interference and single particle tracking analysis of hepatitis C virus endocytosis. PLoS Pathog 5:e1000702 [View Article][PubMed]
    [Google Scholar]
  6. de Lucas S., Peredo J., Marión R. M., Sánchez C., Ortín J. 2010; Human Staufen1 protein interacts with influenza virus ribonucleoproteins and is required for efficient virus multiplication. J Virol 84:7603–7612 [View Article][PubMed]
    [Google Scholar]
  7. den Boon J. A., Ahlquist P. 2010; Organelle-like membrane compartmentalization of positive-strand RNA virus replication factories. Annu Rev Microbiol 64:241–256 [View Article][PubMed]
    [Google Scholar]
  8. Dugré-Brisson S., Elvira G., Boulay K., Chatel-Chaix L., Mouland A. J., DesGroseillers L. 2005; Interaction of Staufen1 with the 5′ end of mRNA facilitates translation of these RNAs. Nucleic Acids Res 33:4797–4812 [View Article][PubMed]
    [Google Scholar]
  9. Emara M. M., Brinton M. A. 2007; Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly. Proc Natl Acad Sci U S A 104:9041–9046 [View Article][PubMed]
    [Google Scholar]
  10. Furic L., Maher-Laporte M., DesGroseillers L. 2008; A genome-wide approach identifies distinct but overlapping subsets of cellular mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein complexes. RNA 14:324–335 [View Article][PubMed]
    [Google Scholar]
  11. Ghoujal B., Milev M. P., Ajamian L., Abel K., Mouland A. J. 2012; ESCRT-II’s involvement in HIV-1 genomic RNA trafficking and assembly. Biol Cell 104:706–721 [View Article][PubMed]
    [Google Scholar]
  12. Harris D., Zhang Z., Chaubey B., Pandey V. N. 2006; Identification of cellular factors associated with the 3′-nontranslated region of the hepatitis C virus genome. Mol Cell Proteomics 5:1006–1018 [View Article][PubMed]
    [Google Scholar]
  13. Kim Y. K., Furic L., Desgroseillers L., Maquat L. E. 2005; Mammalian Staufen1 recruits Upf1 to specific mRNA 3′UTRs so as to elicit mRNA decay. Cell 120:195–208 [View Article][PubMed]
    [Google Scholar]
  14. Kim Y. K., Furic L., Parisien M., Major F., DesGroseillers L., Maquat L. E. 2007; Staufen1 regulates diverse classes of mammalian transcripts. EMBO J 26:2670–2681 [View Article][PubMed]
    [Google Scholar]
  15. Krishnan M. N., Sukumaran B., Pal U., Agaisse H., Murray J. L., Hodge T. W., Fikrig E. 2007; Rab 5 is required for the cellular entry of dengue and West Nile viruses. J Virol 81:4881–4885 [View Article][PubMed]
    [Google Scholar]
  16. Li W., Li Y., Kedersha N., Anderson P., Emara M., Swiderek K. M., Moreno G. T., Brinton M. A. 2002; Cell proteins TIA-1 and TIAR interact with the 3′ stem–loop of the West Nile virus complementary minus-strand RNA and facilitate virus replication. J Virol 76:11989–12000 [View Article][PubMed]
    [Google Scholar]
  17. Ma Y., Anantpadma M., Timpe J. M., Shanmugam S., Singh S. M., Lemon S. M., Yi M. 2011; Hepatitis C virus NS2 protein serves as a scaffold for virus assembly by interacting with both structural and nonstructural proteins. J Virol 85:86–97 [View Article][PubMed]
    [Google Scholar]
  18. Maher-Laporte M., Berthiaume F., Moreau M., Julien L. A., Lapointe G., Mourez M., DesGroseillers L. 2010; Molecular composition of Staufen2-containing ribonucleoproteins in embryonic rat brain. PLoS ONE 5:e11350 [View Article][PubMed]
    [Google Scholar]
  19. Mas A., Alves-Rodrigues I., Noueiry A., Ahlquist P., Díez J. 2006; Host deadenylation-dependent mRNA decapping factors are required for a key step in brome mosaic virus RNA replication. J Virol 80:246–251 [View Article][PubMed]
    [Google Scholar]
  20. Matto M., Sklan E. H., David N., Melamed-Book N., Casanova J. E., Glenn J. S., Aroeti B. 2011; Role for ADP ribosylation factor 1 in the regulation of hepatitis C virus replication. J Virol 85:946–956 [View Article][PubMed]
    [Google Scholar]
  21. Miki T., Takano K., Yoneda Y. 2005; The role of mammalian Staufen on mRNA traffic: a view from its nucleocytoplasmic shuttling function. Cell Struct Funct 30:51–56 [View Article][PubMed]
    [Google Scholar]
  22. Milev M. P., Brown C. M., Mouland A. J. 2010; Live cell visualization of the interactions between HIV-1 Gag and the cellular RNA-binding protein Staufen1. Retrovirology 7:41 [View Article][PubMed]
    [Google Scholar]
  23. Mousseau G., Kota S., Takahashi V., Frick D. N., Strosberg A. D. 2011; Dimerization-driven interaction of hepatitis C virus core protein with NS3 helicase. J Gen Virol 92:101–111 [View Article][PubMed]
    [Google Scholar]
  24. Scheller N., Mina L. B., Galão R. P., Chari A., Giménez-Barcons M., Noueiry A., Fischer U., Meyerhans A., Díez J. 2009; Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates. Proc Natl Acad Sci U S A 106:13517–13522 [View Article][PubMed]
    [Google Scholar]
  25. Tingting P., Caiyun F., Zhigang Y., Pengyuan Y., Zhenghong Y. 2006; Subproteomic analysis of the cellular proteins associated with the 3′ untranslated region of the hepatitis C virus genome in human liver cells. Biochem Biophys Res Commun 347:683–691 [View Article][PubMed]
    [Google Scholar]
  26. Villacé P., Marión R. M., Ortín J. 2004; The composition of Staufen-containing RNA granules from human cells indicates their role in the regulated transport and translation of messenger RNAs. Nucleic Acids Res 32:2411–2420 [View Article][PubMed]
    [Google Scholar]
  27. Wakita T., Pietschmann T., Kato T., Date T., Miyamoto M., Zhao Z., Murthy K., Habermann A., Kräusslich H. G.other authors 2005; Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11:791–796 [View Article][PubMed]
    [Google Scholar]
  28. Wickham L., Duchaîne T., Luo M., Nabi I. R., DesGroseillers L. 1999; Mammalian Staufen is a double-stranded-RNA- and tubulin-binding protein which localizes to the rough endoplasmic reticulum. Mol Cell Biol 19:2220–2230[PubMed]
    [Google Scholar]
  29. Yamasaki S., Stoecklin G., Kedersha N., Simarro M., Anderson P. 2007; T-cell intracellular antigen-1 (TIA-1)-induced translational silencing promotes the decay of selected mRNAs. J Biol Chem 282:30070–30077 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.051383-0
Loading
/content/journal/jgv/10.1099/vir.0.051383-0
Loading

Data & Media loading...

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