The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation

English version

Autoři: Nannan Wu ^aff001; Xuan-Nhi Nguyen ^aff001; Li Wang ^aff002; Romain Appourchaux ^aff001; Chengfei Zhang ^aff002; Baptiste Panthu ^aff001; Henri Gruffat ^aff001; Chloé Journo ^aff001; Sandrine Alais ^aff001; Juliang Qin ^aff002; Na Zhang ^aff002; Kevin Tartour ^aff001; Frédéric Catez ^aff004; Renaud Mahieux ^aff001; Theophile Ohlmann ^aff001; Mingyao Liu ^aff002; Bing Du ^aff002; Andrea Cimarelli ^aff001
Působiště autorů: CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France ^aff001; Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China ^aff002; Shanghai Emerging and Reemerging Infectious Disease Institute, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China ^aff003; Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France ^aff004
Vyšlo v časopise: The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation. PLoS Pathog 15(10): e32767. doi:10.1371/journal.ppat.1008093
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008093

Souhrn

ISG20 is a broad spectrum antiviral protein thought to directly degrade viral RNA. However, this mechanism of inhibition remains controversial. Using the Vesicular Stomatitis Virus (VSV) as a model RNA virus, we show here that ISG20 interferes with viral replication by decreasing protein synthesis in the absence of RNA degradation. Importantly, we demonstrate that ISG20 exerts a translational control over a large panel of non-self RNA substrates including those originating from transfected DNA, while sparing endogenous transcripts. This activity correlates with the protein’s ability to localize in cytoplasmic processing bodies. Finally, these functions are conserved in the ISG20 murine ortholog, whose genetic ablation results in mice with increased susceptibility to viral infection. Overall, our results posit ISG20 as an important defense factor able to discriminate the self/non-self origins of the RNA through translation modulation.

Klíčová slova:

Graphs – Interferons – Luciferase – Messenger RNA – Protein translation – RNA viruses – Transfection – Viral replication

Zdroje

1. Gongora C, David G, Pintard L, Tissot C, Hua TD, Dejean A, et al. Molecular cloning of a new interferon-induced PML nuclear body-associated protein. J Biol Chem. 1997;272(31):19457–63. Epub 1997/08/01. doi: 10.1074/jbc.272.31.19457 9235947.

2. Espert L, Eldin P, Gongora C, Bayard B, Harper F, Chelbi-Alix MK, et al. The exonuclease ISG20 mainly localizes in the nucleolus and the Cajal (Coiled) bodies and is associated with nuclear SMN protein-containing complexes. J Cell Biochem. 2006;98(5):1320–33. Epub 2006/03/04. doi: 10.1002/jcb.20869 16514659.

3. Espert L, Degols G, Gongora C, Blondel D, Williams BR, Silverman RH, et al. ISG20, a new interferon-induced RNase specific for single-stranded RNA, defines an alternative antiviral pathway against RNA genomic viruses. J Biol Chem. 2003;278(18):16151–8. Epub 2003/02/21. doi: 10.1074/jbc.M209628200 12594219.

4. Zuo Y, Deutscher MP. Exoribonuclease superfamilies: structural analysis and phylogenetic distribution. Nucleic Acids Res. 2001;29(5):1017–26. Epub 2001/02/27. doi: 10.1093/nar/29.5.1017 11222749; PubMed Central PMCID: PMC56904.

5. Horio T, Murai M, Inoue T, Hamasaki T, Tanaka T, Ohgi T. Crystal structure of human ISG20, an interferon-induced antiviral ribonuclease. FEBS Lett. 2004;577(1–2):111–6. Epub 2004/11/06. doi: 10.1016/j.febslet.2004.09.074 15527770.

6. Nguyen LH, Espert L, Mechti N, Wilson DM, 3rd. The human interferon- and estrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro. Biochemistry. 2001;40(24):7174–9. Epub 2001/06/13. doi: 10.1021/bi010141t 11401564.

7. Zhang Y, Burke CW, Ryman KD, Klimstra WB. Identification and characterization of interferon-induced proteins that inhibit alphavirus replication. J Virol. 2007;81(20):11246–55. Epub 2007/08/10. doi: 10.1128/JVI.01282-07 17686841; PubMed Central PMCID: PMC2045553.

8. Jiang D, Guo H, Xu C, Chang J, Gu B, Wang L, et al. Identification of three interferon-inducible cellular enzymes that inhibit the replication of hepatitis C virus. J Virol. 2008;82(4):1665–78. Epub 2007/12/14. doi: 10.1128/JVI.02113-07 18077728; PubMed Central PMCID: PMC2258705.

9. Jiang D, Weidner JM, Qing M, Pan XB, Guo H, Xu C, et al. Identification of five interferon-induced cellular proteins that inhibit west nile virus and dengue virus infections. J Virol. 2010;84(16):8332–41. Epub 2010/06/11. doi: 10.1128/JVI.02199-09 20534863; PubMed Central PMCID: PMC2916517.

10. Zhou Z, Wang N, Woodson SE, Dong Q, Wang J, Liang Y, et al. Antiviral activities of ISG20 in positive-strand RNA virus infections. Virology. 2011;409(2):175–88. Epub 2010/11/03. doi: 10.1016/j.virol.2010.10.008 21036379; PubMed Central PMCID: PMC3018280.

11. Weiss CM, Trobaugh DW, Sun C, Lucas TM, Diamond MS, Ryman KD, et al. The Interferon-Induced Exonuclease ISG20 Exerts Antiviral Activity through Upregulation of Type I Interferon Response Proteins. mSphere. 2018;3(5). Epub 2018/09/21. doi: 10.1128/mSphere.00209-18 30232164; PubMed Central PMCID: PMC6147134.

12. Espert L, Degols G, Lin YL, Vincent T, Benkirane M, Mechti N. Interferon-induced exonuclease ISG20 exhibits an antiviral activity against human immunodeficiency virus type 1. J Gen Virol. 2005;86(Pt 8):2221–9. Epub 2005/07/22. doi: 10.1099/vir.0.81074-0 16033969.

13. Leong CR, Funami K, Oshiumi H, Mengao D, Takaki H, Matsumoto M, et al. Interferon-stimulated gene of 20 kDa protein (ISG20) degrades RNA of hepatitis B virus to impede the replication of HBV in vitro and in vivo. Oncotarget. 2016;7(42):68179–93. Epub 2016/09/15. doi: 10.18632/oncotarget.11907 27626689; PubMed Central PMCID: PMC5356548.

14. Qu H, Li J, Yang L, Sun L, Liu W, He H. Influenza A Virus-induced expression of ISG20 inhibits viral replication by interacting with nucleoprotein. Virus Genes. 2016;52(6):759–67. Epub 2016/11/01. doi: 10.1007/s11262-016-1366-2 27342813.

15. Liu Y, Nie H, Mao R, Mitra B, Cai D, Yan R, et al. Interferon-inducible ribonuclease ISG20 inhibits hepatitis B virus replication through directly binding to the epsilon stem-loop structure of viral RNA. PLoS Pathog. 2017;13(4):e1006296. Epub 2017/04/12. doi: 10.1371/journal.ppat.1006296 28399146; PubMed Central PMCID: PMC5388505.

16. Michailidis E, Pabon J, Xiang K, Park P, Ramanan V, Hoffmann HH, et al. A robust cell culture system supporting the complete life cycle of hepatitis B virus. Sci Rep. 2017;7(1):16616. Epub 2017/12/02. doi: 10.1038/s41598-017-16882-5 29192196; PubMed Central PMCID: PMC5709435.

17. Feng J, Wickenhagen A, Turnbull ML, Rezelj VV, Kreher F, Tilston-Lunel NL, et al. Interferon-Stimulated Gene (ISG)-Expression Screening Reveals the Specific Antibunyaviral Activity of ISG20. J Virol. 2018;92(13). Epub 2018/04/27. doi: 10.1128/JVI.02140-17 29695422; PubMed Central PMCID: PMC6002717.

18. Ostertag D, Hoblitzell-Ostertag TM, Perrault J. Cell-type-specific growth restriction of vesicular stomatitis virus polR mutants is linked to defective viral polymerase function. J Virol. 2007;81(2):492–502. Epub 2006/10/27. doi: 10.1128/JVI.01217-06 17065214; PubMed Central PMCID: PMC1797469.

19. Coppotelli G, Mughal N, Callegari S, Sompallae R, Caja L, Luijsterburg MS, et al. The Epstein-Barr virus nuclear antigen-1 reprograms transcription by mimicry of high mobility group A proteins. Nucleic Acids Res. 2013;41(5):2950–62. Epub 2013/01/30. doi: 10.1093/nar/gkt032 23358825; PubMed Central PMCID: PMC3597695.

20. Hebbar PB, Archer TK. Altered histone H1 stoichiometry and an absence of nucleosome positioning on transfected DNA. J Biol Chem. 2008;283(8):4595–601. Epub 2007/12/25. doi: 10.1074/jbc.M709121200 18156629; PubMed Central PMCID: PMC3339569.

21. Glaser R, Zhang HY, Yao KT, Zhu HC, Wang FX, Li GY, et al. Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas. Proc Natl Acad Sci U S A. 1989;86(23):9524–8. Epub 1989/12/01. doi: 10.1073/pnas.86.23.9524 2556716; PubMed Central PMCID: PMC298529.

22. Panthu B, Mure F, Gruffat H, Ohlmann T. In vitro translation of mRNAs that are in their native ribonucleoprotein complexes. Biochem J. 2015;472(1):111–9. Epub 2015/09/10. doi: 10.1042/BJ20150772 26349537.

23. Abbas YM, Pichlmair A, Gorna MW, Superti-Furga G, Nagar B. Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins. Nature. 2013;494(7435):60–4. Epub 2013/01/22. doi: 10.1038/nature11783 23334420; PubMed Central PMCID: PMC4931921.

24. Diamond MS. IFIT1: A dual sensor and effector molecule that detects non-2'-O methylated viral RNA and inhibits its translation. Cytokine Growth Factor Rev. 2014;25(5):543–50. Epub 2014/06/10. doi: 10.1016/j.cytogfr.2014.05.002 24909568; PubMed Central PMCID: PMC4234691.

25. Habjan M, Hubel P, Lacerda L, Benda C, Holze C, Eberl CH, et al. Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA. PLoS Pathog. 2013;9(10):e1003663. Epub 2013/10/08. doi: 10.1371/journal.ppat.1003663 24098121; PubMed Central PMCID: PMC3789756.

26. Pichlmair A, Lassnig C, Eberle CA, Gorna MW, Baumann CL, Burkard TR, et al. IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA. Nat Immunol. 2011;12(7):624–30. Epub 2011/06/07. doi: 10.1038/ni.2048 21642987.

27. Fleith RC, Mears HV, Leong XY, Sanford TJ, Emmott E, Graham SC, et al. IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA. Nucleic Acids Res. 2018;46(10):5269–85. Epub 2018/03/20. doi: 10.1093/nar/gky191 29554348; PubMed Central PMCID: PMC6007307.

28. Li S, Lian SL, Moser JJ, Fritzler ML, Fritzler MJ, Satoh M, et al. Identification of GW182 and its novel isoform TNGW1 as translational repressors in Ago2-mediated silencing. J Cell Sci. 2008;121(Pt 24):4134–44. Epub 2008/12/06. doi: 10.1242/jcs.036905 19056672.

29. Parker R, Sheth U. P bodies and the control of mRNA translation and degradation. Mol Cell. 2007;25(5):635–46. Epub 2007/03/14. doi: 10.1016/j.molcel.2007.02.011 17349952.

30. Genuth NR, Barna M. The Discovery of Ribosome Heterogeneity and Its Implications for Gene Regulation and Organismal Life. Mol Cell. 2018;71(3):364–74. Epub 2018/08/04. doi: 10.1016/j.molcel.2018.07.018 30075139; PubMed Central PMCID: PMC6092941.

31. Boersma S, Khuperkar D, Verhagen BMP, Sonneveld S, Grimm JB, Lavis LD, et al. Multi-Color Single-Molecule Imaging Uncovers Extensive Heterogeneity in mRNA Decoding. Cell. 2019;178(2):458–72 e19. Epub 2019/06/11. doi: 10.1016/j.cell.2019.05.001 31178119; PubMed Central PMCID: PMC6630898.

32. Shi Z, Fujii K, Kovary KM, Genuth NR, Rost HL, Teruel MN, et al. Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide. Mol Cell. 2017;67(1):71–83 e7. Epub 2017/06/20. doi: 10.1016/j.molcel.2017.05.021 28625553; PubMed Central PMCID: PMC5548184.

33. Simsek D, Tiu GC, Flynn RA, Byeon GW, Leppek K, Xu AF, et al. The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity. Cell. 2017;169(6):1051–65 e18. Epub 2017/06/03. doi: 10.1016/j.cell.2017.05.022 28575669; PubMed Central PMCID: PMC5548193.

34. Franz KM, Neidermyer WJ, Tan YJ, Whelan SPJ, Kagan JC. STING-dependent translation inhibition restricts RNA virus replication. Proc Natl Acad Sci U S A. 2018;115(9):E2058–E67. Epub 2018/02/15. doi: 10.1073/pnas.1716937115 29440426; PubMed Central PMCID: PMC5834695.

35. Kumar P, Sweeney TR, Skabkin MA, Skabkina OV, Hellen CU, Pestova TV. Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5'-terminal regions of cap0-, cap1- and 5'ppp- mRNAs. Nucleic Acids Res. 2014;42(5):3228–45. Epub 2013/12/29. doi: 10.1093/nar/gkt1321 24371270; PubMed Central PMCID: PMC3950709.

36. Hui DJ, Bhasker CR, Merrick WC, Sen GC. Viral stress-inducible protein p56 inhibits translation by blocking the interaction of eIF3 with the ternary complex eIF2.GTP.Met-tRNAi. J Biol Chem. 2003;278(41):39477–82. Epub 2003/07/30. doi: 10.1074/jbc.M305038200 12885778.

37. Coller J, Parker R. General translational repression by activators of mRNA decapping. Cell. 2005;122(6):875–86. Epub 2005/09/24. doi: 10.1016/j.cell.2005.07.012 16179257; PubMed Central PMCID: PMC1853273.

38. Bruno I, Wilkinson MF. P-bodies react to stress and nonsense. Cell. 2006;125(6):1036–8. Epub 2006/06/17. doi: 10.1016/j.cell.2006.06.003 16777595.

39. Brengues M, Teixeira D, Parker R. Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science. 2005;310(5747):486–9. Epub 2005/09/06. doi: 10.1126/science.1115791 16141371; PubMed Central PMCID: PMC1863069.

40. Teixeira D, Sheth U, Valencia-Sanchez MA, Brengues M, Parker R. Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA. 2005;11(4):371–82. Epub 2005/02/11. doi: 10.1261/rna.7258505 15703442; PubMed Central PMCID: PMC1370727.

41. Aizer A, Kalo A, Kafri P, Shraga A, Ben-Yishay R, Jacob A, et al. Quantifying mRNA targeting to P-bodies in living human cells reveals their dual role in mRNA decay and storage. J Cell Sci. 2014;127(Pt 20):4443–56. Epub 2014/08/17. doi: 10.1242/jcs.152975 25128566.

42. Decker CJ, Parker R. P-bodies and stress granules: possible roles in the control of translation and mRNA degradation. Cold Spring Harb Perspect Biol. 2012;4(9):a012286. Epub 2012/07/06. doi: 10.1101/cshperspect.a012286 22763747; PubMed Central PMCID: PMC3428773.

43. Luo Y, Na Z, Slavoff SA. P-Bodies: Composition, Properties, and Functions. Biochemistry. 2018;57(17):2424–31. Epub 2018/01/31. doi: 10.1021/acs.biochem.7b01162 29381060.

44. Hubstenberger A, Courel M, Benard M, Souquere S, Ernoult-Lange M, Chouaib R, et al. P-Body Purification Reveals the Condensation of Repressed mRNA Regulons. Mol Cell. 2017;68(1):144–57 e5. Epub 2017/10/03. doi: 10.1016/j.molcel.2017.09.003 28965817.

45. Eulalio A, Behm-Ansmant I, Schweizer D, Izaurralde E. P-body formation is a consequence, not the cause, of RNA-mediated gene silencing. Mol Cell Biol. 2007;27(11):3970–81. Epub 2007/04/04. doi: 10.1128/MCB.00128-07 17403906; PubMed Central PMCID: PMC1900022.

46. Knuckles P, Buhler M. Adenosine methylation as a molecular imprint defining the fate of RNA. FEBS Lett. 2018;592(17):2845–59. Epub 2018/05/22. doi: 10.1002/1873-3468.13107 29782652; PubMed Central PMCID: PMC6175371.

47. Nachtergaele S, He C. Chemical Modifications in the Life of an mRNA Transcript. Annu Rev Genet. 2018. Epub 2018/09/20. doi: 10.1146/annurev-genet-120417-031522 30230927.

48. Jeong S, Stein A. Micrococcal nuclease digestion of nuclei reveals extended nucleosome ladders having anomalous DNA lengths for chromatin assembled on non-replicating plasmids in transfected cells. Nucleic Acids Res. 1994;22(3):370–5. Epub 1994/02/11. doi: 10.1093/nar/22.3.370 7510391; PubMed Central PMCID: PMC523591.

49. Day L, Chau CM, Nebozhyn M, Rennekamp AJ, Showe M, Lieberman PM. Chromatin profiling of Epstein-Barr virus latency control region. J Virol. 2007;81(12):6389–401. Epub 2007/04/06. doi: 10.1128/JVI.02172-06 17409162; PubMed Central PMCID: PMC1900095.

50. Farrell PJ, Balkow K, Hunt T, Jackson RJ, Trachsel H. Phosphorylation of initiation factor elF-2 and the control of reticulocyte protein synthesis. Cell. 1977;11(1):187–200. Epub 1977/05/01. doi: 10.1016/0092-8674(77)90330-0 559547.

51. Levin D, London IM. Regulation of protein synthesis: activation by double-stranded RNA of a protein kinase that phosphorylates eukaryotic initiation factor 2. Proc Natl Acad Sci U S A. 1978;75(3):1121–5. Epub 1978/03/01. doi: 10.1073/pnas.75.3.1121 274704; PubMed Central PMCID: PMC411420.

52. Berger G, Durand S, Fargier G, Nguyen XN, Cordeil S, Bouaziz S, et al. APOBEC3A is a specific inhibitor of the early phases of HIV-1 infection in myeloid cells. PLoS Pathog. 2011;7(9):e1002221. Epub 2011/10/04. doi: 10.1371/journal.ppat.1002221 21966267; PubMed Central PMCID: PMC3178557.

53. Schneider R, Campbell M, Nasioulas G, Felber BK, Pavlakis GN. Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. J Virol. 1997;71(7):4892–903. Epub 1997/07/01. 9188551; PubMed Central PMCID: PMC191719.

54. Landthaler M, Gaidatzis D, Rothballer A, Chen PY, Soll SJ, Dinic L, et al. Molecular characterization of human Argonaute-containing ribonucleoprotein complexes and their bound target mRNAs. RNA. 2008;14(12):2580–96. Epub 2008/11/04. doi: 10.1261/rna.1351608 18978028; PubMed Central PMCID: PMC2590962.

55. Ricci EP, Limousin T, Soto-Rifo R, Rubilar PS, Decimo D, Ohlmann T. miRNA repression of translation in vitro takes place during 43S ribosomal scanning. Nucleic Acids Res. 2013;41(1):586–98. Epub 2012/11/20. doi: 10.1093/nar/gks1076 23161679; PubMed Central PMCID: PMC3592420.

56. Medina-Palazon C, Gruffat H, Mure F, Filhol O, Vingtdeux-Didier V, Drobecq H, et al. Protein kinase CK2 phosphorylation of EB2 regulates its function in the production of Epstein-Barr virus infectious viral particles. J Virol. 2007;81(21):11850–60. Epub 2007/08/19. doi: 10.1128/JVI.01421-07 17699575; PubMed Central PMCID: PMC2168784.

57. Gruffat H, Manet E, Rigolet A, Sergeant A. The enhancer factor R of Epstein-Barr virus (EBV) is a sequence-specific DNA binding protein. Nucleic Acids Res. 1990;18(23):6835–43. Epub 1990/12/11. doi: 10.1093/nar/18.23.6835 2175879; PubMed Central PMCID: PMC332739.

58. Delecluse HJ, Hilsendegen T, Pich D, Zeidler R, Hammerschmidt W. Propagation and recovery of intact, infectious Epstein-Barr virus from prokaryotic to human cells. Proc Natl Acad Sci U S A. 1998;95(14):8245–50. Epub 1998/07/08. doi: 10.1073/pnas.95.14.8245 9653172; PubMed Central PMCID: PMC20961.

59. Jaitin DA, Roisman LC, Jaks E, Gavutis M, Piehler J, Van der Heyden J, et al. Inquiring into the differential action of interferons (IFNs): an IFN-alpha2 mutant with enhanced affinity to IFNAR1 is functionally similar to IFN-beta. Mol Cell Biol. 2006;26(5):1888–97. Epub 2006/02/16. doi: 10.1128/MCB.26.5.1888-1897.2006 16479007; PubMed Central PMCID: PMC1430259.

60. Li R, Tan B, Yan Y, Ma X, Zhang N, Zhang Z, et al. Extracellular UDP and P2Y6 function as a danger signal to protect mice from vesicular stomatitis virus infection through an increase in IFN-beta production. J Immunol. 2014;193(9):4515–26. Epub 2014/09/28. doi: 10.4049/jimmunol.1301930 25261483.

61. Belin S, Hacot S, Daudignon L, Therizols G, Pourpe S, Mertani HC, et al. Purification of ribosomes from human cell lines. Curr Protoc Cell Biol. 2010;Chapter 3:Unit 3 40. Epub 2010/12/15. doi: 10.1002/0471143030.cb0340s49 21154551.