1887

Abstract

Heterogeneous nuclear ribonucleoproteins A and B (hnRNPs A/B), cellular RNA-binding proteins that participate in splicing, trafficking, translation and turnover of mRNAs, have been implicated in the life cycles of several cytoplasmic RNA viruses. Here, we demonstrate that silencing of hnRNPs A1 and A2 significantly reduces the replication of the arenavirus Junín virus (JUNV), the aetiological agent of Argentine haemorrhagic fever. While acute JUNV infection did not modify total levels of expression of hnRNPs A/B in comparison with uninfected cells, non-cytopathic persistent infection exhibited low levels of these cell proteins. Furthermore, acutely infected cells showed a cytoplasmic relocalization of overexpressed hnRNP A1, probably related to the involvement of this protein in virus replicative cycle. This cytoplasmic accumulation was also observed in cells expressing viral nucleoprotein (N), and co-immunoprecipitation studies revealed the interaction between hnRNP A1 and N protein. By contrast, a predominantly nuclear distribution of overexpressed hnRNP A1 was found during persistent infection, even in the presence of endogenous or overexpressed N protein, indicating a differential modulation of nucleo–cytoplasmic trafficking in acute and persistent JUNV infections.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.030163-0
2011-09-01
2020-01-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/9/2181.html?itemId=/content/journal/jgv/10.1099/vir.0.030163-0&mimeType=html&fmt=ahah

References

  1. Agis-Juárez R. A., Galván I., Medina F. J., Daikoku T., Padmanabhan R., Ludert J. E., del Angel R. M.. ( 2009;). Polypyrimidine tract-binding protein is relocated to the cytoplasm and is required during dengue virus infection in Vero cells. . J Gen Virol 90:, 2893–2901. [CrossRef][PubMed]
    [Google Scholar]
  2. Allemand E., Guil S., Myers M., Moscat J., Cáceres J. F., Krainer A. R.. ( 2005;). Regulation of heterogenous nuclear ribonucleoprotein A1 transport by phosphorylation in cells stressed by osmotic shock. . Proc Natl Acad Sci U S A 102:, 3605–3610. [CrossRef][PubMed]
    [Google Scholar]
  3. Artuso M. C., Ellenberg P. C., Scolaro L. A., Damonte E. B., García C. C.. ( 2009;). Inhibition of Junín virus replication by small interfering RNAs. . Antiviral Res 84:, 31–37. [CrossRef][PubMed]
    [Google Scholar]
  4. Bowick G. C., Spratt H. M., Hogg A. E., Endsley J. J., Wiktorowicz J. E., Kurosky A., Luxon B. A., Gorenstein D. G., Herzog N. K.. ( 2009;). Analysis of the differential host cell nuclear proteome induced by attenuated and virulent hemorrhagic arenavirus infection. . J Virol 83:, 687–700. [CrossRef][PubMed]
    [Google Scholar]
  5. Brunner J. E., Nguyen J. H., Roehl H. H., Ho T. V., Swiderek K. M., Semler B. L.. ( 2005;). Functional interaction of heterogeneous nuclear ribonucleoprotein C with poliovirus RNA synthesis initiation complexes. . J Virol 79:, 3254–3266. [CrossRef][PubMed]
    [Google Scholar]
  6. Burnham A. J., Gong L., Hardy R. W.. ( 2007;). Heterogeneous nuclear ribonuclear protein K interacts with Sindbis virus nonstructural proteins and viral subgenomic mRNA. . Virology 367:, 212–221. [CrossRef][PubMed]
    [Google Scholar]
  7. Cammas A., Pileur F., Bonnal S., Lewis S. M., Lévêque N., Holcik M., Vagner S.. ( 2007;). Cytoplasmic relocalization of heterogeneous nuclear ribonucleoprotein A1 controls translation initiation of specific mRNAs. . Mol Biol Cell 18:, 5048–5059. [CrossRef][PubMed]
    [Google Scholar]
  8. Caputi M., Mayeda A., Krainer A. R., Zahler A. M.. ( 1999;). hnRNP A/B proteins are required for inhibition of HIV-1 pre-mRNA splicing. . EMBO J 18:, 4060–4067. [CrossRef][PubMed]
    [Google Scholar]
  9. Charrel R. N., de Lamballerie X.. ( 2010;). Zoonotic aspects of arenavirus infections. . Vet Microbiol 140:, 213–220. [CrossRef][PubMed]
    [Google Scholar]
  10. Cheunim T., Zhang J., Milligan S. G., McPhillips M. G., Graham S. V.. ( 2008;). The alternative splicing factor hnRNP A1 is up-regulated during virus-infected epithelial cell differentiation and binds the human papillomavirus type 16 late regulatory element. . Virus Res 131:, 189–198. [CrossRef][PubMed]
    [Google Scholar]
  11. Dreyfuss G., Kim V. N., Kataoka N.. ( 2002;). Messenger-RNA-binding proteins and the messages they carry. . Nat Rev Mol Cell Biol 3:, 195–205. [CrossRef][PubMed]
    [Google Scholar]
  12. Ellenberg P., Edreira M., Lozano M., Scolaro L. A.. ( 2002;). Synthesis and expression of viral antigens in Vero cells persistently infected with . Junín virus. . Arch Virol 147:, 1543–1557. [CrossRef][PubMed]
    [Google Scholar]
  13. Ellenberg P., Edreira M., Scolaro L. A.. ( 2004;). Resistance to superinfection of Vero cells persistently infected with . Junín virus. . Arch Virol 149:, 507–522. [CrossRef][PubMed]
    [Google Scholar]
  14. Ellenberg P., Linero F. N., Scolaro L. A.. ( 2007;). Superinfection exclusion in BHK-21 cells persistently infected with Junín virus. . J Gen Virol 88:, 2730–2739. [CrossRef][PubMed]
    [Google Scholar]
  15. Florez P. M., Sessions O. M., Wagner E. J., Gromeier M., Garcia-Blanco M. A.. ( 2005;). The polypyrimidine tract binding protein is required for efficient picornavirus gene expression and propagation. . J Virol 79:, 6172–6179. [CrossRef][PubMed]
    [Google Scholar]
  16. Frieman M., Yount B., Heise M., Kopecky-Bromberg S. A., Palese P., Baric R. S.. ( 2007;). Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. . J Virol 81:, 9812–9824. [CrossRef][PubMed]
    [Google Scholar]
  17. Gui H., Lu C.-W., Adams S., Stollar V., Li M.-L.. ( 2010;). hnRNP A1 interacts with the genomic and subgenomic RNA promoters of Sindbis virus and is required for the synthesis of G and SG RNA. . J Biomed Sci 17:, 59. [CrossRef][PubMed]
    [Google Scholar]
  18. Guil S., Long J. C., Cáceres J. F.. ( 2006;). hnRNP A1 relocalization to the stress granules reflects a role in the stress response. . Mol Cell Biol 26:, 5744–5758. [CrossRef][PubMed]
    [Google Scholar]
  19. Gustin K. E.. ( 2003;). Inhibition of nucleo-cytoplasmic trafficking by RNA viruses: targeting the nuclear pore complex. . Virus Res 95:, 35–44. [CrossRef][PubMed]
    [Google Scholar]
  20. Gustin K. E., Sarnow P.. ( 2001;). Effects of poliovirus infection on nucleo-cytoplasmic trafficking and nuclear pore complex composition. . EMBO J 20:, 240–249. [CrossRef][PubMed]
    [Google Scholar]
  21. Kafasla P., Morgner N., Robinson C. V., Jackson R. J.. ( 2010;). Polypyrimidine tract-binding protein stimulates the poliovirus IRES by modulating eIF4G binding. . EMBO J 29:, 3710–3722. [CrossRef][PubMed]
    [Google Scholar]
  22. Kim C. S., Seol S. K., Song O. K., Park J. H., Jang S. K.. ( 2007;). An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication. . J Virol 81:, 3852–3865. [CrossRef][PubMed]
    [Google Scholar]
  23. Lee K. J., Novella I. S., Teng M. N., Oldstone M. B., de La Torre J. C.. ( 2000;). NP and L proteins of lymphocytic choriomeningitis virus (LCMV) are sufficient for efficient transcription and replication of LCMV genomic RNA analogs. . J Virol 74:, 3470–3477. [CrossRef][PubMed]
    [Google Scholar]
  24. Lewis S. M., Veyrier A., Hosszu Ungureanu N., Bonnal S., Vagner S., Holcik M.. ( 2007;). Subcellular relocalization of a trans-acting factor regulates XIAP IRES-dependent translation. . Mol Biol Cell 18:, 1302–1311. [CrossRef][PubMed]
    [Google Scholar]
  25. Lin J. Y., Li M. L., Huang P. N., Chien K. Y., Horng J. T., Shih S. R.. ( 2008;). Heterogeneous nuclear ribonuclear protein K interacts with the enterovirus 71 5′ untranslated region and participates in virus replication. . J Gen Virol 89:, 2540–2549. [CrossRef][PubMed]
    [Google Scholar]
  26. Lin J. Y., Shih S. R., Pan M., Li C., Lue C. F., Stollar V., Li M. L.. ( 2009;). hnRNP A1 interacts with the 5′ untranslated regions of enterovirus 71 and Sindbis virus RNA and is required for viral replication. . J Virol 83:, 6106–6114. [CrossRef][PubMed]
    [Google Scholar]
  27. Linero F. N., Scolaro L. A.. ( 2009;). Participation of the phosphatidylinositol 3-kinase/Akt pathway in Junín virus replication in vitro. . Virus Res 145:, 166–170. [CrossRef][PubMed]
    [Google Scholar]
  28. López N., Jácamo R., Franze-Fernández M. T.. ( 2001;). Transcription and RNA replication of tacaribe virus genome and antigenome analogs require N and L proteins: Z protein is an inhibitor of these processes. . J Virol 75:, 12241–12251. [CrossRef][PubMed]
    [Google Scholar]
  29. Martínez-Sobrido L., Zúñiga E. I., Rosario D., García-Sastre A., de la Torre J. C.. ( 2006;). Inhibition of the type I interferon response by the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus. . J Virol 80:, 9192–9199. [CrossRef][PubMed]
    [Google Scholar]
  30. Martínez-Sobrido L., Giannakas P., Cubitt B., García-Sastre A., de la Torre J. C.. ( 2007;). Differential inhibition of type I interferon induction by arenavirus nucleoproteins. . J Virol 81:, 12696–12703. [CrossRef][PubMed]
    [Google Scholar]
  31. Mayeda A., Munroe S. H., Cáceres J. F., Krainer A. R.. ( 1994;). Function of conserved domains of hnRNP A1 and other hnRNP A/B proteins. . EMBO J 13:, 5483–5495.[PubMed]
    [Google Scholar]
  32. Perera R., Daijogo S., Walter B. L., Nguyen J. H., Semler B. L.. ( 2007;). Cellular protein modification by poliovirus: the two faces of poly(rC)-binding protein. . J Virol 81:, 8919–8932. [CrossRef][PubMed]
    [Google Scholar]
  33. Pettit Kneller E. L., Connor J. H., Lyles D. S. J.. ( 2009;). hnRNPs relocalize to the cytoplasm following infection with vesicular stomatitis virus. . J Virol 83:, 770–780. [CrossRef][PubMed]
    [Google Scholar]
  34. Pleschka S.. ( 2008;). RNA viruses and the mitogenic Raf/MEK/ERK signal transduction cascade. . Biol Chem 389:, 1273–1282. [CrossRef][PubMed]
    [Google Scholar]
  35. Reid S. P., Leung L. W., Hartman A. L., Martinez O., Shaw M. L., Carbonnelle C., Volchkov V. E., Nichol S. T., Basler C. F.. ( 2006;). Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation. . J Virol 80:, 5156–5167. [CrossRef][PubMed]
    [Google Scholar]
  36. Rodriguez J. J., Wang L. F., Horvath C. M.. ( 2003;). Hendra virus V protein inhibits interferon signaling by preventing STAT1 and STAT2 nuclear accumulation. . J Virol 77:, 11842–11845. [CrossRef][PubMed]
    [Google Scholar]
  37. Romanelli M. G., Morandi C.. ( 2002;). Importin α binds to an unusual bipartite nuclear localization signal in the heterogeneous ribonucleoprotein type I. . Eur J Biochem 269:, 2727–2734. [CrossRef][PubMed]
    [Google Scholar]
  38. Sánchez A., Pifat D. Y., Kenyon R. H., Peters C. J., McCormick J. B., Kiley M. P.. ( 1989;). Junín virus monoclonal antibodies: characterization and cross-reactivity with other arenaviruses. . J Gen Virol 70:, 1125–1132. [CrossRef][PubMed]
    [Google Scholar]
  39. Sawicka K., Bushell M., Spriggs K. A., Willis A. E.. ( 2008;). Polypyrimidine-tract-binding protein: a multifunctional RNA-binding protein. . Biochem Soc Trans 36:, 641–647. [CrossRef][PubMed]
    [Google Scholar]
  40. Seo Y. J., Blake C., Alexander S., Hahm B.. ( 2010;). Sphingosine 1-phosphate-metabolizing enzymes control influenza virus propagation and viral cytopathogenicity. . J Virol 84:, 8124–8131. [CrossRef][PubMed]
    [Google Scholar]
  41. Shi S. T., Huang P., Li H. P., Lai M. M.. ( 2000;). Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus. . EMBO J 19:, 4701–4711. [CrossRef][PubMed]
    [Google Scholar]
  42. Shi S. T., Yu G. Y., Lai M. M.. ( 2003;). Multiple type A/B heterogeneous nuclear ribonucleoproteins (hnRNPs) can replace hnRNP A1 in mouse hepatitis virus RNA synthesis. . J Virol 77:, 10584–10593. [CrossRef][PubMed]
    [Google Scholar]
  43. Walter B. L., Nguyen J. H., Ehrenfeld E., Semler B. L.. ( 1999;). Differential utilization of poly(rC) binding protein 2 in translation directed by picornavirus IRES elements. . RNA 5:, 1570–1585. [CrossRef][PubMed]
    [Google Scholar]
  44. Yun N. E., Linde N. S., Dziuba N., Zacks M. A., Smith J. N., Smith J. K., Aronson J. F., Chumakova O. V., Lander H. M. et al. ( 2008;). Pathogenesis of XJ and Romero strains of . Junín virus in two strains of guinea pigs. . Am J Trop Med Hyg 79:, 275–282.[PubMed]
    [Google Scholar]
  45. Zhao T. T., Graber T. E., Jordan L. E., Cloutier M., Lewis S. M., Goulet I., Côté J., Holcik M.. ( 2009;). hnRNP A1 regulates UV-induced NF-κB signalling through destabilization of cIAP1 mRNA. . Cell Death Differ 16:, 244–252. [CrossRef][PubMed]
    [Google Scholar]
  46. Zúñiga S., Sola I., Cruz J. L., Enjuanes L.. ( 2009;). Role of RNA chaperones in virus replication. . Virus Res 139:, 253–266. [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.030163-0
Loading
/content/journal/jgv/10.1099/vir.0.030163-0
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