Influenza A H3N2 subtype virus NS1 protein targets into the nucleus and binds primarily via its C-terminal NLS2/NoLS to nucleolin and fibrillarin

详细信息    查看全文

• 作者：Krister Melén (1)
  Janne Tynell (1)
  Riku Fagerlund (2)
  Pascal Roussel (3)
  Danièle Hernandez-Verdun (4)
  Ilkka Julkunen (1)
  
• 关键词：Influenza A virus ; NS1 protein ; NoLS ; Nucleolus ; Nucleolin ; B23 ; Fibrillarin
• 刊名：Virology Journal
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：9
• 期：1
• 全文大小：3028KB
• 参考文献：1. Jagger BW, Wise HM, Kash JC, Walters KA, Wills NM, Xiao YL, Dunfee RL, Schwartzman LM, Ozinsky A, Bell GL, / et al.: An Overlapping Protein-Coding Region in Influenza A Virus Segment 3 Modulates the Host Response. / Science 2012, 337:119-04. CrossRef
  2. Kawaoka Y, Gorman OT, Ito T, Wells K, Donis RO, Castrucci MR, Donatelli I, Webster RG: Influence of host species on the evolution of the nonstructural (NS) gene of influenza A viruses. / Virus Res 1998, 55:143-56. CrossRef
  3. Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, Sessions WM, Xu X, Skepner E, Deyde V, / et al.: Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. / Science 2009, 325:197-01. CrossRef
  4. Min JY, Krug RM: The primary function of RNA binding by the influenza A virus NS1 protein in infected cells: Inhibiting the 2'-5' oligo (A) synthetase/RNase L pathway. / Proc Natl Acad Sci U S A 2006, 103:7100-105. CrossRef
  5. Mibayashi M, Martinez-Sobrido L, Loo YM, Cardenas WB, Gale M Jr, Garcia-Sastre A: Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. / J Virol 2007, 81:514-24. CrossRef
  6. Pichlmair A, Schulz O, Tan CP, Naslund TI, Liljestrom P, Weber F, Reis e Sousa C: RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates. / Science 2006, 314:997-001. CrossRef
  7. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, / et al.: Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. / Nature 2006, 441:101-05. CrossRef
  8. Matikainen S, Siren J, Tissari J, Veckman V, Pirhonen J, Severa M, Sun Q, Lin R, Meri S, Uze G, / et al.: Tumor necrosis factor alpha enhances influenza A virus-induced expression of antiviral cytokines by activating RIG-I gene expression. / J Virol 2006, 80:3515-522. CrossRef
  9. Siren J, Imaizumi T, Sarkar D, Pietila T, Noah DL, Lin R, Hiscott J, Krug RM, Fisher PB, Julkunen I, Matikainen S: Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines. / Microbes Infect 2006, 8:2013-020. CrossRef
  10. Chen Z, Li Y, Krug RM: Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery. / EMBO J 1999, 18:2273-283. CrossRef
  11. Li Y, Chen ZY, Wang W, Baker CC, Krug RM: The 3'-end-processing factor CPSF is required for the splicing of single-intron pre-mRNAs in vivo. / RNA 2001, 7:920-31. CrossRef
  12. Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM: Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. / Mol Cell 1998, 1:991-000. CrossRef
  13. Noah DL, Twu KY, Krug RM: Cellular antiviral responses against influenza A virus are countered at the posttranscriptional level by the viral NS1A protein via its binding to a cellular protein required for the 3' end processing of cellular pre-mRNAS. / Virology 2003, 307:386-95. CrossRef
  14. Shimizu K, Iguchi A, Gomyou R, Ono Y: Influenza virus inhibits cleavage of the HSP70 pre-mRNAs at the polyadenylation site. / Virology 1999, 254:213-19. CrossRef
  15. Twu KY, Noah DL, Rao P, Kuo RL, Krug RM: The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target. / J Virol 2006, 80:3957-965. CrossRef
  16. Min JY, Li S, Sen GC, Krug RM: A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis. / Virology 2007, 363:236-43. CrossRef
  17. Heikkinen LS, Kazlauskas A, Melen K, Wagner R, Ziegler T, Julkunen I, Saksela K: Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL Src homology 3 domains to activate host cell signaling. / J Biol Chem 2008, 283:5719-727. CrossRef
  18. Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, Farzan M, Inoue S, Jung JU, Garcia-Sastre A: Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. / Cell Host Microbe 2009, 5:439-49. CrossRef
  19. Li S, Min JY, Krug RM, Sen GC: Binding of the influenza A virus NS1 protein to PKR mediates the inhibition of its activation by either PACT or double-stranded RNA. / Virology 2006, 349:13-1. CrossRef
  20. Bornholdt ZA, Prasad BV: X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus. / Nature 2008, 456:985-88. CrossRef
  21. Hale BG, Batty IH, Downes CP, Randall RE: Binding of influenza A virus NS1 protein to the inter-SH2 domain of p85 suggests a novel mechanism for phosphoinositide 3-kinase activation. / J Biol Chem 2008, 283:1372-380. CrossRef
  22. Boisvert FM, van Koningsbruggen S, Navascues J, Lamond AI: The multifunctional nucleolus. / Nat Rev Mol Cell Biol 2007, 8:574-85. CrossRef
  23. Hernandez-Verdun D, Roussel P, Thiry M, Sirri V, Lafontaine DL: The nucleolus: structure/function relationship in RNA metabolism. / Wiley Interdiscip Rev RNA 2010, 1:415-31. CrossRef
  24. Olson MO: Sensing cellular stress: another new function for the nucleolus? / Sci STKE 2004, 2004:pe10. CrossRef
  25. Olson MO, Hingorani K, Szebeni A: Conventional and nonconventional roles of the nucleolus. / Int Rev Cytol 2002, 219:199-66. CrossRef
  26. Pederson T, Tsai RY: In search of nonribosomal nucleolar protein function and regulation. / J Cell Biol 2009, 184:771-76. CrossRef
  27. Carmo-Fonseca M: The contribution of nuclear compartmentalization to gene regulation. / Cell 2002, 108:513-21. CrossRef
  28. Emmott E, Hiscox JA: Nucleolar targeting: the hub of the matter. / EMBO Rep 2009, 10:231-38. CrossRef
  29. Hiscox JA: RNA viruses: hijacking the dynamic nucleolus. / Nat Rev Microbiol 2007, 5:119-27. CrossRef
  30. Olson MO, Dundr M: The moving parts of the nucleolus. / Histochem Cell Biol 2005, 123:203-16. CrossRef
  31. Quaye IK, Toku S, Tanaka T: Sequence requirement for nucleolar localization of rat ribosomal protein L31. / Eur J Cell Biol 1996, 69:151-55.
  32. Macken C, Lu H, Goodman J, Boykin L: The value of a database in surveillance and vaccine selection. In / Options for the Control of Influenza IV. Edited by: Osterhaus ADME, Cox N, Hampson AW. Elsevier Science, Amsterdam; 2001:103-06.
  33. Timmers AC, Stuger R, Schaap PJ, van 't Riet J, Raue HA: Nuclear and nucleolar localization of Saccharomyces cerevisiae ribosomal proteins S22 and S25. / FEBS Lett 1999, 452:335-40. CrossRef
  34. Birbach A, Bailey ST, Ghosh S, Schmid JA: Cytosolic, nuclear and nucleolar localization signals determine subcellular distribution and activity of the NF-kappaB inducing kinase NIK. / J Cell Sci 2004, 117:3615-624. CrossRef
  35. Lechertier T, Sirri V, Hernandez-Verdun D, Roussel P: A B23-interacting sequence as a tool to visualize protein interactions in a cellular context. / J Cell Sci 2007, 120:265-75. CrossRef
  36. Sirri V, Urcuqui-Inchima S, Roussel P, Hernandez-Verdun D: Nucleolus: the fascinating nuclear body. / Histochem Cell Biol 2008, 129:13-1. CrossRef
  37. Melen K, Kinnunen L, Fagerlund R, Ikonen N, Twu KY, Krug RM, Julkunen I: Nuclear and nucleolar targeting of influenza A virus NS1 protein: striking differences between different virus subtypes. / J Virol 2007, 81:5995-006. CrossRef
  38. Murayama R, Harada Y, Shibata T, Kuroda K, Hayakawa S, Shimizu K, Tanaka T: Influenza A virus non-structural protein 1 (NS1) interacts with cellular multifunctional protein nucleolin during infection. / Biochem Biophys Res Commun 2007, 362:880-85. CrossRef
  39. Li Y, Yamakita Y, Krug RM: Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. / Proc Natl Acad Sci U S A 1998, 95:4864-869. CrossRef
  40. Cochrane AW, Perkins A, Rosen CA: Identification of sequences important in the nucleolar localization of human immunodeficiency virus Rev: relevance of nucleolar localization to function. / J Virol 1990, 64:881-85.
  41. Fankhauser C, Izaurralde E, Adachi Y, Wingfield P, Laemmli UK: Specific complex of human immunodeficiency virus type 1 rev and nucleolar B23 proteins: dissociation by the Rev response element. / Mol Cell Biol 1991, 11:2567-575.
  42. Perkins A, Cochrane AW, Ruben SM, Rosen CA: Structural and functional characterization of the human immunodeficiency virus rev protein. / J Acquir Immune Defic Syndr 1989, 2:256-63.
  43. Qin XF, An DS, Chen IS, Baltimore D: Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. / Proc Natl Acad Sci U S A 2003, 100:183-88. CrossRef
  44. Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J: Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. / Cancer Res 1982, 42:3858-863.
  45. Neumann G, Watanabe T, Ito H, Watanabe S, Goto H, Gao P, Hughes M, Perez DR, Donis R, Hoffmann E, / et al.: Generation of influenza A viruses entirely from cloned cDNAs. / Proc Natl Acad Sci U S A 1999, 96:9345-350. CrossRef
  46. Gaush CR, Smith TF: Replication and plaque assay of influenza virus in an established line of canine kidney cells. / Appl Microbiol 1968, 16:588-94.
  47. Malim MH, Cullen BR: HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency. / Cell 1991, 65:241-48. CrossRef
  48. Malim MH, Hauber J, Fenrick R, Cullen BR: Immunodeficiency virus rev trans-activator modulates the expression of the viral regulatory genes. / Nature 1988, 335:181-83. CrossRef
  49. Ogawa H, Inouye S, Tsuji FI, Yasuda K, Umesono K: Localization, trafficking, and temperature-dependence of the Aequorea green fluorescent protein in cultured vertebrate cells. / Proc Natl Acad Sci U S A 1995, 92:11899-1903. CrossRef
  50. Fagerlund R, Kinnunen L, Kohler M, Julkunen I, Melen K: NF-{kappa}B is transported into the nucleus by importin {alpha}3 and importin {alpha}4. / J Biol Chem 2005, 280:15942-5951. CrossRef
  
• 作者单位：Krister Melén (1)
  Janne Tynell (1)
  Riku Fagerlund (2)
  Pascal Roussel (3)
  Danièle Hernandez-Verdun (4)
  Ilkka Julkunen (1)
  
  1. Virology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare (THL), Mannerheimintie 166, FIN-00300, Helsinki, Finland
  2. Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA
  3. Functional Organization of the Nucleolus, RNA Biology-FRE 3402 CNRS, Université Pierre et Marie Curie, 75252, Paris cedex 5, France
  4. Nuclei and Cell Cycle, Institut Jacques Monod-UMR 7592 CNRS, Université Paris Diderot, 75205, Paris cedex 13, France
  
• ISSN：1743-422X

文摘

Background Influenza A virus non-structural protein 1 (NS1) is a virulence factor, which is targeted into the cell cytoplasm, nucleus and nucleolus. NS1 is a multi-functional protein that inhibits host cell pre-mRNA processing and counteracts host cell antiviral responses. Previously, we have shown that the NS1 protein of the H3N2 subtype influenza viruses possesses a C-terminal nuclear localization signal (NLS) that also functions as a nucleolar localization signal (NoLS) and targets the protein into the nucleolus. Results Here, we show that the NS1 protein of the human H3N2 virus subtype interacts in vitro primarily via its C-terminal NLS2/NoLS and to a minor extent via its N-terminal NLS1 with the nucleolar proteins, nucleolin and fibrillarin. Using chimeric green fluorescence protein (GFP)-NS1 fusion constructs, we show that the nucleolar retention of the NS1 protein is determined by its C-terminal NLS2/NoLS in vivo. Confocal laser microscopy analysis shows that the NS1 protein colocalizes with nucleolin in nucleoplasm and nucleolus and with B23 and fibrillarin in the nucleolus of influenza A/Udorn/72 virus-infected A549 cells. Since some viral proteins contain NoLSs, it is likely that viruses have evolved specific nucleolar functions. Conclusion NS1 protein of the human H3N2 virus interacts primarily via the C-terminal NLS2/NoLS and to a minor extent via the N-terminal NLS1 with the main nucleolar proteins, nucleolin, B23 and fibrillarin.