1887

Abstract

NS1 proteins of influenza A and B viruses share limited sequence homology, yet both are potent manipulators of host cell processes, particularly interferon (IFN) induction. Although many cellular partners are reported for A/NS1, only a few (e.g. PKR and ISG15) have been identified for B/NS1. Here, affinity-purification and mass spectrometry were used to expand the known host interactome of B/NS1. We identified 22 human proteins as new putative targets for B/NS1, validating several, including DHX9, ILF3, YBX1 and HNRNPC. Consistent with two RNA-binding domains in B/NS1, many of the identified factors bind RNA and some interact with B/NS1 in an RNA-dependent manner. Functional characterization of several B/NS1 interactors identified SNRNP200 as a potential positive regulator of host IFN responses, while ILF3 exhibited dual roles in both IFN induction and influenza B virus replication. These data provide a resource for future investigations into the mechanisms underpinning host cell modulation by influenza B virus NS1.

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2017-09-01
2024-03-29
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References

  1. Koutsakos M, Nguyen TH, Barclay WS, Kedzierska K. Knowns and unknowns of influenza B viruses. Future Microbiol 2016; 11:119–135 [View Article][PubMed]
    [Google Scholar]
  2. Palese P, Shaw ML. Orthomyxoviridae: the viruses and their replication. In Knipe DM, Howley PM. (editors) Fields Virology Lippincott Williams & Wilkins; 2013 pp. 1151–1185
    [Google Scholar]
  3. Dauber B, Heins G, Wolff T. The influenza B virus nonstructural NS1 protein is essential for efficient viral growth and antagonizes beta interferon induction. J Virol 2004; 78:1865–1872 [View Article][PubMed]
    [Google Scholar]
  4. Dauber B, Schneider J, Wolff T. Double-stranded RNA binding of influenza B virus nonstructural NS1 protein inhibits protein kinase R but is not essential to antagonize production of alpha/beta interferon. J Virol 2006; 80:11667–11677 [View Article][PubMed]
    [Google Scholar]
  5. Zhao C, Sridharan H, Chen R, Baker DP, Wang S et al. Influenza B virus non-structural protein 1 counteracts ISG15 antiviral activity by sequestering ISGylated viral proteins. Nat Commun 2016; 7:12754 [View Article][PubMed]
    [Google Scholar]
  6. Krug RM. Functions of the influenza A virus NS1 protein in antiviral defense. Curr Opin Virol 2015; 12:1–6 [View Article][PubMed]
    [Google Scholar]
  7. Jackson D, Elderfield RA, Barclay WS. Molecular studies of influenza B virus in the reverse genetics era. J Gen Virol 2011; 92:1–17 [View Article][PubMed]
    [Google Scholar]
  8. Donelan NR, Dauber B, Wang X, Basler CF, Wolff T et al. The N- and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and beta interferon promoter activation. J Virol 2004; 78:11574–11582 [View Article][PubMed]
    [Google Scholar]
  9. Hale BG. Conformational plasticity of the influenza A virus NS1 protein. J Gen Virol 2014; 95:2099–2105 [View Article][PubMed]
    [Google Scholar]
  10. Wang W, Krug RM. The RNA-binding and effector domains of the viral NS1 protein are conserved to different extents among influenza A and B viruses. Virology 1996; 223:41–50 [View Article][PubMed]
    [Google Scholar]
  11. Yin C, Khan JA, Swapna GV, Ertekin A, Krug RM et al. Conserved surface features form the double-stranded RNA binding site of non-structural protein 1 (NS1) from influenza A and B viruses. J Biol Chem 2007; 282:20584–20592 [View Article][PubMed]
    [Google Scholar]
  12. 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; 307:386–395 [View Article][PubMed]
    [Google Scholar]
  13. Ehrhardt C, Wolff T, Ludwig S. Activation of phosphatidylinositol 3-kinase signaling by the nonstructural NS1 protein is not conserved among type A and B influenza viruses. J Virol 2007; 81:12097–12100 [View Article][PubMed]
    [Google Scholar]
  14. Hale BG, Jackson D, Chen YH, Lamb RA, Randall RE. Influenza A virus NS1 protein binds p85β and activates phosphatidylinositol-3-kinase signaling. Proc Natl Acad Sci USA 2006; 103:14194–14199 [View Article][PubMed]
    [Google Scholar]
  15. Yuan W, Krug RM. Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. Embo J 2001; 20:362–371 [View Article][PubMed]
    [Google Scholar]
  16. Guan R, Ma LC, Leonard PG, Amer BR, Sridharan H et al. Structural basis for the sequence-specific recognition of human ISG15 by the NS1 protein of influenza B virus. Proc Natl Acad Sci USA 2011; 108:13468–13473 [View Article][PubMed]
    [Google Scholar]
  17. Versteeg GA, Hale BG, van Boheemen S, Wolff T, Lenschow DJ et al. Species-specific antagonism of host ISGylation by the influenza B virus NS1 protein. J Virol 2010; 84:5423–5430 [View Article][PubMed]
    [Google Scholar]
  18. Kochs G, García-Sastre A, Martínez-Sobrido L. Multiple anti-interferon actions of the influenza A virus NS1 protein. J Virol 2007; 81:7011–7021 [View Article][PubMed]
    [Google Scholar]
  19. Ayllon J, Domingues P, Rajsbaum R, Miorin L, Schmolke M et al. A single amino acid substitution in the novel H7N9 influenza A virus NS1 protein increases CPSF30 binding and virulence. J Virol 2014; 88:12146–12151 [View Article][PubMed]
    [Google Scholar]
  20. Melén K, Kinnunen L, Fagerlund R, Ikonen N, Twu KY et al. Nuclear and nucleolar targeting of influenza A virus NS1 protein: striking differences between different virus subtypes. J Virol 2007; 81:5995–6006 [View Article][PubMed]
    [Google Scholar]
  21. Schneider J, Dauber B, Melén K, Julkunen I, Wolff T. Analysis of influenza B Virus NS1 protein trafficking reveals a novel interaction with nuclear speckle domains. J Virol 2009; 83:701–711 [View Article][PubMed]
    [Google Scholar]
  22. Hilton L, Moganeradj K, Zhang G, Chen YH, Randall RE et al. The NPro product of bovine viral diarrhea virus inhibits DNA binding by interferon regulatory factor 3 and targets it for proteasomal degradation. J Virol 2006; 80:11723–11732 [View Article][PubMed]
    [Google Scholar]
  23. Didcock L, Young DF, Goodbourn S, Randall RE. The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation. J Virol 1999; 73:9928–9933[PubMed]
    [Google Scholar]
  24. Chang YG, Yan XZ, Xie YY, Gao XC, Song AX et al. Different roles for two ubiquitin-like domains of ISG15 in protein modification. J Biol Chem 2008; 283:13370–13377 [View Article][PubMed]
    [Google Scholar]
  25. Dauber B, Martínez-Sobrido L, Schneider J, Hai R, Waibler Z et al. Influenza B virus ribonucleoprotein is a potent activator of the antiviral kinase PKR. PLoS Pathog 2009; 5:e1000473 [View Article][PubMed]
    [Google Scholar]
  26. Pichlmair A, Kandasamy K, Alvisi G, Mulhern O, Sacco R et al. Viral immune modulators perturb the human molecular network by common and unique strategies. Nature 2012; 487:486–490 [View Article][PubMed]
    [Google Scholar]
  27. Sadewasser A, Saenger S, Paki K, Schwecke T, Wolff T. Disruption of Src homology 3-binding motif within non-structural protein 1 of influenza B virus unexpectedly enhances viral replication in human cells. J Gen Virol 2016; 97:2856–2867 [View Article][PubMed]
    [Google Scholar]
  28. Patel RC, Vestal DJ, Xu Z, Bandyopadhyay S, Guo W et al. DRBP76, a double-stranded RNA-binding nuclear protein, is phosphorylated by the interferon-induced protein kinase, PKR. J Biol Chem 1999; 274:20432–20437 [View Article][PubMed]
    [Google Scholar]
  29. Landthaler M, Gaidatzis D, Rothballer A, Chen PY, Soll SJ et al. Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs. RNA 2008; 14:2580–2596 [View Article][PubMed]
    [Google Scholar]
  30. Shabman RS, Gulcicek EE, Stone KL, Basler CF. The Ebola virus VP24 protein prevents hnRNP C1/C2 binding to karyopherin α1 and partially alters its nuclear import. J Infect Dis 2011; 204:S904–S910 [View Article][PubMed]
    [Google Scholar]
  31. Lyabin DN, Eliseeva IA, Ovchinnikov LP. YB-1 protein: functions and regulation. Wiley Interdiscip Rev RNA 2014; 5:95–110 [View Article][PubMed]
    [Google Scholar]
  32. Kawaguchi A, Matsumoto K, Nagata K. YB-1 functions as a porter to lead influenza virus ribonucleoprotein complexes to microtubules. J Virol 2012; 86:11086–11095 [View Article][PubMed]
    [Google Scholar]
  33. Kawaguchi A, Hirohama M, Harada Y, Osari S, Nagata K. Influenza virus induces cholesterol-enriched endocytic recycling compartments for budozone formation via cell cycle-independent centrosome maturation. PLoS Pathog 2015; 11:e1005284 [View Article][PubMed]
    [Google Scholar]
  34. Ma LC, Guan R, Hamilton K, Aramini JM, Mao L et al. A second RNA-binding site in the NS1 protein of nfluenza B virus. Structure 2016; 24:1562–1572 [View Article][PubMed]
    [Google Scholar]
  35. Jiang J, Li J, Fan W, Zheng W, Yu M et al. Robust Lys63-linked ubiquitination of RIG-I promotes cytokine eruption in early influenza B virus infection. J Virol 2016; 90:6263–6275 [View Article][PubMed]
    [Google Scholar]
  36. Chen S, Short JA, Young DF, Killip MJ, Schneider M et al. Heterocellular induction of interferon by negative-sense RNA viruses. Virology 2010; 407:247–255 [View Article][PubMed]
    [Google Scholar]
  37. Tremblay N, Baril M, Chatel-Chaix L, Es-Saad S, Park AY et al. Spliceosome SNRNP200 promotes viral RNA sensing and IRF3 activation of antiviral response. PLoS Pathog 2016; 12:e1005772 [View Article][PubMed]
    [Google Scholar]
  38. Bortz E, Westera L, Maamary J, Steel J, Albrecht RA et al. Host- and strain-specific regulation of influenza virus polymerase activity by interacting cellular proteins. MBio 2011; 2:e00151-11 [View Article][PubMed]
    [Google Scholar]
  39. Wang P, Song W, Mok BW, Zhao P, Qin K et al. Nuclear factor 90 negatively regulates influenza virus replication by interacting with viral nucleoprotein. J Virol 2009; 83:7850–7861 [View Article][PubMed]
    [Google Scholar]
  40. Wen X, Huang X, Mok BW, Chen Y, Zheng M et al. NF90 exerts antiviral activity through regulation of PKR phosphorylation and stress granules in infected cells. J Immunol 2014; 192:3753–3764 [View Article][PubMed]
    [Google Scholar]
  41. Isken O, Baroth M, Grassmann CW, Weinlich S, Ostareck DH et al. Nuclear factors are involved in hepatitis C virus RNA replication. RNA 2007; 13:1675–1692 [View Article][PubMed]
    [Google Scholar]
  42. Isken O, Grassmann CW, Sarisky RT, Kann M, Zhang S et al. Members of the NF90/NFAR protein group are involved in the life cycle of a positive-strand RNA virus. Embo J 2003; 22:5655–5665 [View Article][PubMed]
    [Google Scholar]
  43. Gomila RC, Martin GW, Gehrke L. NF90 binds the dengue virus RNA 3' terminus and is a positive regulator of dengue virus replication. PLoS One 2011; 6:e16687 [View Article][PubMed]
    [Google Scholar]
  44. Li Y, Masaki T, Shimakami T, Lemon SM. hnRNP L and NF90 interact with hepatitis C virus 5'-terminal untranslated RNA and promote efficient replication. J Virol 2014; 88:7199–7209 [View Article][PubMed]
    [Google Scholar]
  45. Shabman RS, Leung DW, Johnson J, Glennon N, Gulcicek EE et al. DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function. J Infect Dis 2011; 204:S911–S918 [View Article][PubMed]
    [Google Scholar]
  46. Patiño C, Haenni AL, Urcuqui-Inchima S. NF90 isoforms, a new family of cellular proteins involved in viral replication?. Biochimie 2015; 108:20–24 [View Article][PubMed]
    [Google Scholar]
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