1887

Abstract

It has previously been shown that influenza virus NS1 protein enhances the translation of viral but not cellular mRNAs. This enhancement occurs by increasing the rate of translation initiation and requires the 5′UTR sequence, common to all viral mRNAs. In agreement with these findings, we show here that viral mRNAs, but not cellular mRNAs, are associated with NS1 during virus infection. We have previously reported that NS1 interacts with the translation initiation factor eIF4GI, next to its poly(A)-binding protein 1 (PABP1)-interacting domain and that NS1 and eIF4GI are associated in influenza virus-infected cells. Here we show that NS1, although capable of binding poly(A), does not compete with PABP1 for association with eIF4GI and, furthermore, that NS1 and PABP1 interact both and in an RNA-independent manner. The interaction maps between residues 365 and 535 in PABP1 and between residues 1 and 81 in NS1. These mapping studies, together with those previously reported for NS1–eIF4GI and PABP1–eIF4GI interactions, imply that the binding of all three proteins would be compatible. Collectively, these and previously published data suggest that NS1 interactions with eIF4GI and PABP1, as well as with viral mRNAs, could promote the specific recruitment of 43S complexes to the viral mRNAs.

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2003-12-01
2024-04-18
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References

  1. Adam S. A., Nakagawa T., Swanson M. S., Woodruff T. K., Dreyfuss G. 1986; mRNA polyadenylate-binding protein: gene isolation and sequencing and identification of a ribonucleoprotein consensus sequence. Mol Cell Biol 6:2932–2943
    [Google Scholar]
  2. Aragón T., de la Luna S., Novoa I., Carrasco L., Ortín J., Nieto A. 2000; Eukaryotic translation initiation factor 4GI is a cellular target for NS1 protein, a translational activator of influenza virus. Mol Cell Biol 20:6259–6268
    [Google Scholar]
  3. Barret S. C., Brown T. C. M., Almond J. W. 1979; The smallest genome RNA segment of influenza virus contains two genes that may overlap. Proc Natl Acad Sci U S A 76:3790–3794
    [Google Scholar]
  4. Beloso A., Martínez C., Valcárcel J., Fernández-Santarén J., Ortín J. 1992; Degradation of cellular mRNA during influenza virus infection: its possible role in protein synthesis shutoff. J Gen Virol 73:575–581
    [Google Scholar]
  5. Bonneau A. M., Sonenberg N. 1987; Proteolysis of the p220 component of the cap-binding protein complex is not sufficient for complete inhibition of host cell protein synthesis after poliovirus infection. J Virol 61:986–991
    [Google Scholar]
  6. Buratti E., Tisminetzky S., Zotti M., Baralle F. E. 1998; Functional analysis of the interaction between HCV 5′ UTR and putative subunits of eukaryotic translation initiation factor 3IF3. Nucleic Acids Res 26:3179–3187
    [Google Scholar]
  7. Burd C. G., Matunis E. L., Dreyfus G. 1991; The multiple RNA-binding domains of the mRNA poly A-binding protein have different RNA-binding activities. Mol Cell Biol 11:3419–3424
    [Google Scholar]
  8. Chen Z., Li Y., Krug R. M. 1999; Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3′-end processing machinery. EMBO J 18:2273–2283
    [Google Scholar]
  9. Craig A. W. B., Haghighat A., Yu A. T. K., Sonenberg N. 1998; Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation. Nature 392:520–523
    [Google Scholar]
  10. de la Luna S., Fortes P., Beloso A., Ortin J. 1995; Influenza virus NS1 protein enhances the rate of translation initiation of viral mRNAs. J Virol 69:2427–2433
    [Google Scholar]
  11. Egorov A., Brandt S., Sereinig S., Romanova J., Ferko B., Katinger D., Grassauer A., Alexandrova G., Katinger H., Muster T. 1998; Transfectant influenza A viruses with long deletions in the NS1 protein grow efficiently in Vero cells. J Virol 72:6437–6441
    [Google Scholar]
  12. Enami K., Sato T. A., Nakada S., Enami M. 1994; Influenza virus NS1 protein stimulates translation of the M1 protein. J Virol 68:1432–1437
    [Google Scholar]
  13. Estes M. K., Cohen J. 1989; Rotavirus gene structure and function. Microbiol Rev 53:440–449
    [Google Scholar]
  14. Etchison D., Milburn S. C., Edery I., Sonenberg N., Kaufman R. J. 1982; Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with the proteolysis of a 220,000-dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex. J Biol Chem 257:14806–14810
    [Google Scholar]
  15. Falcón A., Fortes P., Marión R. M., Beloso A., Ortín J. 1999; Interaction of influenza virus NS1 protein and the human homologue of Staufen in vivo and in vitro. Nucleic Acids Res 27:2241–2247
    [Google Scholar]
  16. Fortes P., Beloso A., Ortín J. 1994; Influenza virus NS1 protein inhibits pre-mRNA splicing and blocks RNA nucleocytoplasmic transport. EMBO J 13:704–712
    [Google Scholar]
  17. Garfinkel M. S., Katze M. G. 1993; Translational control by influenza virus. Selective translation is mediated by sequences within the viral mRNA 5′-untranslated region. J Biol Chem 268:22223–22226
    [Google Scholar]
  18. Gluzman Y. 1981; SV40 transformed simian cells support the replication of early SV40 mutants. Cell 23:175–182
    [Google Scholar]
  19. Grange T., Martins de Sa C., Oddos J., Pictet R. 1987; Human mRNA polyadenylate binding protein: evolutionary conservation of a nucleic acid binding protein. Nucleic Acids Res 15:4771–4787
    [Google Scholar]
  20. Gray N. K., Coller J. M., Dickson K. S., Wickens M. 2000; Multiple portions of poly(A)-binding protein stimulate translation in vivo . EMBO J 19:4723–4733
    [Google Scholar]
  21. Hatada E., Fukuda R. 1992; Binding of influenza A virus NS1 protein to dsRNA in vitro . J Gen Virol 73:3325–3329
    [Google Scholar]
  22. Hatada E., Saito S., Okishio N., Fukuda R. 1997; Binding of the influenza virus NS1 protein to model genome RNAs. J Gen Virol 78:1059–1063
    [Google Scholar]
  23. Hoshino S., Imai M., Kobayashi T., Uchida N., Katada T. 1999; The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3′-poly(A) tail of mRNA. J Biol Chem 274:16677–16680
    [Google Scholar]
  24. Imataka H., Gradi A., Sonenberg N. 1998; A newly identified N-terminal amino acid sequence of human eIF4G binds poly(A)-binding protein and functions in poly(A)-dependent translation. EMBO J 17:7480–7489
    [Google Scholar]
  25. Inglis S. C. 1982; Inhibition of host protein synthesis and degradation of cellular mRNAs during infection by influenza and Herpes simplex virus. Mol Cell Biol 2:1644–1648
    [Google Scholar]
  26. Irurzun A., Sanchez-Palomino S., Novoa I., Carrasco L. 1995; Monensin and nigericin prevent the inhibition of host translation by poliovirus without affecting p220 cleavage. J Virol 69:7453–7460
    [Google Scholar]
  27. Jackson R. J., Kaminski A. 1995; Internal initiation of translation in eukaryotes: the picornaviral paradigm and beyond. RNA 1:985–1000
    [Google Scholar]
  28. Joachims M., Van Breugel P. C., LLoyd R. 1999; Cleavage of poly(A)-binding protein by enterovirus proteases concurrent with inhibition of translation in vitro. J Virol 73:718–727
    [Google Scholar]
  29. Katze M. G., DeCorato D., Krug R. M. 1986; Cellular mRNA translation is blocked at both initiation and elongation after infection by influenza virus or adenovirus. J Virol 60:1027–1039
    [Google Scholar]
  30. Keiper B. D., Rhoads R. E. 1997; Cap-independent translation initiation in Xenopus oocytes. Nucleic Acids Res 25:395–403
    [Google Scholar]
  31. Kerekatte V., Keiper B. D., Badorff C., Cai A., Knowlton K. U., Rhoads R. E. 1999; Cleavage of poly(A)-binding protein by coxsackievirus 2A protease in vitro and in vivo: another mechanism for host protein synthesis shutoff?. J Virol 73:709–717
    [Google Scholar]
  32. Kessler S. H., Sachs A. 1998; RNA recognition motif 2 of yeast Pab1p is required for its functional interaction with eukaryotic translation initiation factor 4G. Mol Cell Biol 18:51–57
    [Google Scholar]
  33. Khaleghpour K., Kahvejian A., De Crescenzo G., Roy G., Svitkin Y. V., Imataka H., O'Connor-McCourt M., Sonenberg N. 2001; Dual interactions of the translational repressor Paip2 with poly(A) binding protein. Mol Cell Biol 21:5200–5213
    [Google Scholar]
  34. Krug R. M., Etkind P. R. 1973; Cytoplasmic and nuclear specific proteins in influenza virus-infected MDCK cells. Virology 56:334–348
    [Google Scholar]
  35. Krug R. M., Broni B. A., Bouloy M. 1979; Are the 5′-ends of influenza viral mRNAs synthesized in vivo donated by host mRNAs?. Cell 18:329–334
    [Google Scholar]
  36. Kühn U., Pieler T. 1996; Xenopus poly(A) binding protein: functional domains in RNA binding and protein–protein interaction. J Mol Biol 256:20–30
    [Google Scholar]
  37. Lamb R. A., Choppin P. W. 1979; Segment 8 of the influenza virus genome is unique in coding for two polypeptides. Proc Natl Acad Sci U S A 76:4908–4912
    [Google Scholar]
  38. Lamphear B. J., Rhoads R. E. 1996; A single amino acid change in protein synthesis initiation factor 4G renders cap-dependent translation resistant to picornaviral 2A proteases. Biochemistry 35:15726–15733
    [Google Scholar]
  39. Lee T. G., Tomita J., Hovanessian A. G., Katze M. G. 1992; Characterization and regulation of the 58,000-dalton cellular inhibitor of the interferon-induced, dsRNA-activated protein kinase. J Biol Chem 267:14238–14243
    [Google Scholar]
  40. Li Y., Chen Z. Y., Wang W., Baker C. C., Krug R. M. 2001; The 3′-end-processing factor CPSF is required for the splicing of single-intron pre-mRNA in vivo. RNA 7:920–931
    [Google Scholar]
  41. Lopez de Quinto S., Martinez-Salas E. 2000; Interaction of the eIF4GI initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo. RNA 6:1380–1392
    [Google Scholar]
  42. Lu Y., Wambach M., Katze M. G., Krug R. M. 1995; Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor. Virology 214:222–228
    [Google Scholar]
  43. Luo G. X., Luytjes W., Enami M., Palese P. 1991; The polyadenylation signal of influenza virus RNA involves a stretch of uridines followed by the RNA duplex of the panhandle structure. J Virol 65:2861–2867
    [Google Scholar]
  44. Marión R. M., Aragón T., Beloso A., Nieto A., Ortín J. 1997a; The N-terminal half of the influenza virus NS1 protein is sufficient for nuclear retention of mRNA and enhancement of viral mRNA translation. Nucleic Acids Res 25:4271–4277
    [Google Scholar]
  45. Marión R. M., Zurcher T., de la Luna S., Ortin J. 1997b; Influenza virus NS1 protein interacts with viral transcription–replication complexes in vivo . J Gen Virol 78:2447–2451
    [Google Scholar]
  46. Marión R. M., Fortes P., Beloso A., Dotti C., Ortín J. 1999; A human sequence homologue of Staufen is an RNA binding protein that is associated to polysomes and localizes to the rough endoplasmic reticulum. Mol Cell Biol 19:2212–2219
    [Google Scholar]
  47. Meyer K., Petersen A., Niepmann M., Beck E. 1995; Interaction of eukaryotic initiation factor eIF-4B with a picornavirus internal translation initiation site. J Virol 69:2819–2824
    [Google Scholar]
  48. Nemeroff M. E., Barabino S. M., Li Y., Keller W., Krug R. M. 1998; Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3′ end formation of cellular pre-mRNAs. Mol Cell 1:991–1000
    [Google Scholar]
  49. Nieto A., de la Luna S., Bárcena J., Portela A., Valcárcel J., Melero J. A., Ortín J. 1992; Nuclear transport of influenza virus polymerase PA protein. Virus Res 24:65–75
    [Google Scholar]
  50. Noah D. L., Twu K. Y., Krug R. M. 2003; 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 307:386–395
    [Google Scholar]
  51. Ortín J., Nájera R., López C., Dávila M., Domingo E. 1980; Genetic variability of Hong Kong (H3N2) influenza viruses: spontaneous mutations and their location in the viral genome. Gene 11:319–331
    [Google Scholar]
  52. Park Y. W., Katze M. G. 1995; Translational control by influenza virus. Identification of cis-acting sequences and trans-acting factors which may regulate selective viral mRNA translation. J Biol Chem 270:28433–28439
    [Google Scholar]
  53. Park Y. W., Wilusz J., Katze M. G. 1999; Regulation of eukaryotic protein synthesis: selective influenza viral mRNA translation is mediated by the cellular RNA-binding protein GRSF-1. Proc Natl Acad Sci U S A 96:6694–6699
    [Google Scholar]
  54. Perales B., Ortín J. 1997; The influenza A virus PB2 polymerase subunit is required for the replication of viral RNA. J Virol 71:1381–1385
    [Google Scholar]
  55. Pestova T. V., Hellen C. U. T. 1999; Ribosome recruitment and scanning: what's new?. Trends Biochem Sci 24:85–87
    [Google Scholar]
  56. Pestova T. V., Shatsky I. N., Fletcher S. P., Jackson R. J., Hellen C. U. T. 1998; A prokaryotic-like mode of cytoplasmic eukaryotic ribosome binding to the initiation codon during internal translation initiation of hepatic C and classical swine fever virus RNAs. Genes Dev 12:67–83
    [Google Scholar]
  57. Piron M., Vende P., Cohen J., Poncet D. 1998; Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F. EMBO J 17:5811–5821
    [Google Scholar]
  58. Polyak S. J., Tang N., Wambach M., Barber G. N., Katze M. G. 1996; The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity. J Biol Chem 271:1702–1707
    [Google Scholar]
  59. Poon L. M., Pritlove D. C., Sharp J., Brownlee G. G. 1998; The RNA polymerase of influenza virus, bound to the 5′ end of virion RNA, acts in cis to polyadenylate mRNA. J Virol 72:8214–8219
    [Google Scholar]
  60. Poon L. L., Pritlove D. C., Fodor E., Brownlee G. G. 1999; Direct evidence that the poly(A) tail of influenza A virus mRNA is synthesized by reiterative copying of a U track in the virion RNA template. J Virol 73:3473–3476
    [Google Scholar]
  61. Qiu Y., Krug R. M. 1994; The influenza virus NS1 protein is a poly(A)-binding protein that inhibits nuclear export of mRNAs containing poly(A. J Virol 68:2425–2432
    [Google Scholar]
  62. Qiu Y., Nemeroff M., Krug R. M. 1995; The influenza virus NS1 protein binds to a specific region in human U6 snRNA and inhibits U6–U2 and U6–U4 snRNA interactions during splicing. RNA 1:304–316
    [Google Scholar]
  63. Robertson J. S., Schubert M., Lazzarini R. A. 1981; Polyadenylation sites for influenza mRNA. J Virol 38:157–163
    [Google Scholar]
  64. Roy G., De Crescenzo G., Khaleghpour K., Kahvejian A., O'Connor-McCourt M., Sonenberg N. 2002; Paip1 interacts with poly A binding protein though two independent binding motifs. Mol Cell Biol 22:3769–3782
    [Google Scholar]
  65. Sachs A. B., Bond M. W., Kornberg R. D. 1986; A single gene from yeast for both nuclear and cytoplasmic polyadenylated-binding protein: domain structure and expression. Cell 45:827–835
    [Google Scholar]
  66. Salvatore M., Basler C. F., Parisien J.-P., Horvath C. M., Bourmakina S., Zheng H., Muster T., Palese P., García-Sastre A. 2002; Effects of influenza A virus NS1 protein on protein expression: the NS1 protein enhances translation and is not required for shutoff of host protein synthesis. J Virol 76:1206–1212
    [Google Scholar]
  67. Sanz-Ezquerro J. J., de la Luna S., Ortín J., Nieto A. 1995; Individual expression of influenza virus PA protein induces degradation of coexpressed proteins. J Virol 69:2420–2426
    [Google Scholar]
  68. Skehel J. J. 1972; Polypeptide synthesis in influenza-virus infected cells. Virology 49:23–36
    [Google Scholar]
  69. Talon J., Horvath C. M., Polley R., Basler C. F., Muster T., Palese P., García-Sastre A. 2000; Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. J Virol 74:7989–7996
    [Google Scholar]
  70. Tarun S. Z., Sachs A. B. 1996; Association of the yeast poly(A) tail binding protein with translation initiation factor eIF4G. EMBO J 15:7168–7177
    [Google Scholar]
  71. Tarun S. Z. J., Wells S. E., Deardoff J. A., Sachs A. B. 1997; Translation initiation factor eIF4G mediates in vitro poly(A)-dependent translation. Proc Natl Acad Sci U S A 94:9046–9051
    [Google Scholar]
  72. Vende P., Piron M., Castagne N., Poncet D. 2000; Efficient translation of rotavirus mRNA requires simultaneous interaction of NSP3 with the eukaryotic translation initiation factor eIF4G and the mRNA 3′ end. J Virol 74:7064–7071
    [Google Scholar]
  73. Wakiyama M., Imataka H., Sonenberg N. 2000; Interaction of eIF4G with poly(A)-binding protein stimulates translation and is critical for Xenopus oocyte maturation. Current Biology 10:1147–1150
    [Google Scholar]
  74. Wang X., Ullah Z., Grumet R. 2000a; Interaction between zucchini yellow mosaic potyvirus RNA-dependent RNA polymerase and host poly-(A) binding protein. Virology 275:433–443
    [Google Scholar]
  75. Wang X., Li M., Zheng H., Muster T., Palese P., Beg A. García-Sastre 2000b; Influenza A virus NS1 protein prevents activation of NF- κ B and induction of alpha/beta interferon. J Virol 74:11566–11573
    [Google Scholar]
  76. Wolff T., O'Neill R. E., Palese P. 1998; NS1-binding protein (NS1-BP): a novel human protein that interacts with the influenza A virus nonstructural NS1 protein is relocalized in the nuclei of infected cells. J Virol 72:7170–7180
    [Google Scholar]
  77. Zelus B. D., Giebelhaus D. H., Eib D. W., Kenner K., Moon R. T. 1989; Expression of the poly(A)-binding protein during development of Xenopus laevis . Mol Cell Biol 9:2756–2760
    [Google Scholar]
  78. Zürcher T., Marión R. M., Ortín J. 2000; Protein synthesis shut-off induced by influenza virus infection is independent of PKR activity. J Virol 74:8781–8784
    [Google Scholar]
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