Toscana virus non-structural protein NSs acts as E3 ubiquitin ligase promoting RIG-I degradation


Autoři: Gianni Gori Savellini aff001;  Gabriele Anichini aff001;  Claudia Gandolfo aff001;  Shibily Prathyumnan aff001;  Maria Grazia Cusi aff001
Působiště autorů: Department of Medical Biotechnologies, University of Siena, Siena, Italy aff001
Vyšlo v časopise: Toscana virus non-structural protein NSs acts as E3 ubiquitin ligase promoting RIG-I degradation. PLoS Pathog 15(12): e1008186. doi:10.1371/journal.ppat.1008186
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1008186

Souhrn

It is known that the non-structural protein (NSs) of Toscana virus (TOSV), an emergent sandfly-borne virus causing meningitis or more severe central nervous system injuries in humans, exerts its function triggering RIG-I for degradation in a proteasome-dependent manner, thus breaking off the IFN-β production. The non-structural protein of different members of Bunyavirales has recently appeared as a fundamental protagonist in immunity evasion through ubiquitination-mediated protein degradation targets. We showed that TOSV NSs has an E3 ubiquitin ligase activity, mapping at the carboxy-terminal domain and also involving the amino-terminal of the protein. Indeed, neither the amino- (NSsΔN) nor the carboxy- (NSsΔC) terminal-deleted mutants of TOSV NSs were able to cause ubiquitin-mediated proteasome degradation of RIG-I. Moreover, the addition of the C-terminus of TOSV NSs to the homologous protein of the Sandfly Fever Naples Virus, belonging to the same genus and unable to inhibit IFN-β activity, conferred new properties to this protein, favoring RIG-I ubiquitination and its degradation. NSs lost its antagonistic activity to IFN when one of the terminal residues was missing. Therefore, we showed that NSs could behave as an atypical RING between RING (RBR) E3 ubiquitin ligases. This is the first report which identified the E3 ubiquitin ligase activity in a viral protein among negative strand RNA viruses.

Klíčová slova:

293T cells – Cysteine – Immunoblotting – Ligases – Luciferase – Recombinant proteins – Ubiquitin ligases – Ubiquitination


Zdroje

1. Braito A, Ciufolini MG, Pippi L, Corbisiero R, Fiorentini C, Gistri A, et al. Phlebotomus-transmitted Toscana virus infections of the central nervous system: a seven-year experience in Tuscany. Scand J Infect Dis. 1998;30: 505–508. doi: 10.1080/00365549850161539 10066054

2. Verani P, Ciufolini MG, Nicoletti L, Calducci M, Sabatinelli G, Coluzzi M, Paci P, et al. Ecological and epidemiological studies of Toscana virus, an arbovirus isolated from Phlebotomus. Ann Ist Super Sanità. 1982;18: 397–399. 7187828

3. Kuhn J, Bewermeyer H, Hartmann-Klosterkoetter U, Emmerich P, Schilling S, Valassina M. Toscana virus causing severe meningoencephalitis in an elderly traveler. J Neurol Neurosurg Psychatry. 2005;76: 1605–1606.

4. Bartels S, Heckmann JG. Lethal encephalitis caused by Toscana virus in an elderly patient. J Neurol. 2012;259: 175–177. doi: 10.1007/s00415-011-6121-y 21656341

5. Sanbonmatsu-Gámez S, Pérez-Ruiz M, Palop-Borrás B, Navarro-Marí JM. Unusual manifestation of Toscana virus infection, Spain. Emerg Infect Dis. 2009;15: 347–348 doi: 10.3201/eid1502.081001 19193294

6. Bouloy M. Bunyaviridae: genome organization and replication strategies. Adv Virus Res. 1991;40: 235–75 doi: 10.1016/s0065-3527(08)60281-x 1957720

7. Di Bonito P, Mochi S, Grò MC, Fortini D, Giorgi C. Organization of the M genomic segment of Toscana phlebovirus. J Gen Virol. 1997;76: 77–81.

8. Accardi L, Gro MC, Di Bonito P, Giorgi C. Toscana virus genomic L segment: molecular cloning, coding strategy and amino acid sequence in comparison with other negative strand RNA viruses. Virus Res. 1993;27: 119–131. doi: 10.1016/0168-1702(93)90076-y 8460526

9. Grò MC, Di Bonito P, Fortini D, Mochi S, Giorgi C. Completion of molecular characterization of Toscana phlebovirus genome: nucleotide sequence, coding strategy of M genomic segment and its amino acid sequence comparison to other phleboviruses. Virus Res. 1997;51: 81–91. doi: 10.1016/s0168-1702(97)00076-2 9381797

10. Reikine S, Nguyen JB, Modis Y. Pattern Recognition and Signaling Mechanisms of RIG-I and MDA5. Front Immunol. 2014;5: 342. doi: 10.3389/fimmu.2014.00342 25101084

11. Weber F, Bridgen A, Fazakerley JK, Streitenfeld H, Kessler N, Randall RE, et al. Bunyamwera bunyavirus nonstructural protein NSs counteracts the induction of alpha/beta interferon. J Virol. 2002;76: 7949–7955. doi: 10.1128/JVI.76.16.7949-7955.2002 12133999

12. Jääskeläinen KM, Kaukinen P, Minskaya ES, Plyusnina A, Vapalahti O, Elliott RM, et al. Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter. J Med Virol. 2007;79: 1527–1536. doi: 10.1002/jmv.20948 17705180

13. Bridgen AM, Weber F, Fazakerley JK, Elliott RM. Bunyamvera bunyavirus non-structural protein NSs is nonessential gene product that contributes to the viral pathogenesis. Proc Natl Acad Sci. 2001;98: 664–669. doi: 10.1073/pnas.98.2.664 11209062

14. Blakqori G, Delhaye S, Habjan M, Blair CD, Sánchez-Vargas I, Olson KE, et al. La Crosse bunyavirus nonstructural protein NSs serves to suppress the type I interferon system of mammalian hosts. J Virol. 2007;81: 4991–4999. doi: 10.1128/JVI.01933-06 17344298

15. Léonard VH, Kohl A, Hart TJ, Elliott RM. Interaction of Bunyamwera Orthobunyavirus NSs protein with mediator protein MED8: a mechanism for inhibiting the interferon response. J Virol. 2006;80: 9667–9675. doi: 10.1128/JVI.00822-06 16973571

16. Wuerth JD, Weber F. Phleboviruses and the Type I Interferon Response. Viruses. 2016;8:pii: E174.

17. Brisbarre NM, Plumet S, de Micco P, Leparc-Goffart I, Emonet SF. Toscana virus inhibits the interferon beta response in cell cultures. Virology. 2013;442: 189–194. doi: 10.1016/j.virol.2013.04.016 23684418

18. Gori Savellini G, Weber F, Terrosi C, Habjan M, Martorelli B, Cusi MG. Toscana virus induces interferon although its NSs protein reveals antagonistic activity. J Gen Virol. 2011;92: 71–79. doi: 10.1099/vir.0.025999-0 20861320

19. Chen X, Ye H, Li S, Jiao B, Wu J, Zeng P, et al. Severe fever with thrombocytopenia syndrome virus inhibits exogenous Type I IFN signaling pathway through its NSs in vitro. PLoS One. 2017;12: e0172744. doi: 10.1371/journal.pone.0172744 28234991

20. Zhang S, Zheng B, Wang T, Li A, Wan J, Qu J, et al. NSs protein of severe fever with thrombocytopenia syndrome virus suppresses interferon production through different mechanism than Rift Valley fever virus. Acta Virol. 2017;61: 289–298. doi: 10.4149/av_2017_307 28854793

21. Gori Savellini G, Valentini M, Cusi MG. Toscana virus NSs protein inhibits the induction of type I interferon by interacting with RIG-I. J Virol. 2013;87: 6660–6667. doi: 10.1128/JVI.03129-12 23552410

22. Gori Savellini G, Gandolfo C, Cusi MG. Truncation of the C-terminal region of Toscana Virus NSs protein is critical for interferon-β antagonism and protein stability. Virology. 2015;486: 255–262. doi: 10.1016/j.virol.2015.09.021 26474372

23. Pickart CM. Mechanisms underlying ubiquitination. Annu Rev Biochem. 2001;70: 503–533. doi: 10.1146/annurev.biochem.70.1.503 11395416

24. Scheffner M, Nuber U, Huibregtse JM. Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature. 1995;373: 81–83. doi: 10.1038/373081a0 7800044

25. Ardley HC, Robinson PA. E3 ubiquitin ligases. Essays Biochem. 2005;41: 15–30. 16250895

26. Bernassola F, Karin M, Ciechanover A, Melino G. The HECT family of E3 ubiquitin ligases: multiple players in cancer development. Cancer Cell. 2008;14: 10–21. doi: 10.1016/j.ccr.2008.06.001 18598940

27. Bosu DR, Kipreos ET. Cullin-RING ubiquitin ligases: global regulation and activation cycles. Cell Div. 2008;3: 7. doi: 10.1186/1747-1028-3-7 18282298

28. Zheng N, Shabek N. Ubiquitin Ligases: Structure, Function, and Regulation. Annu Rev Biochem. 2017;86: 129–157. doi: 10.1146/annurev-biochem-060815-014922 28375744

29. Jackson PK, Eldridge AG, Freed E, Furstenthal L, Hsu JY, Kaiser BK, et al. The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases. Trends Cell Biol. 2000;10: 429–439. doi: 10.1016/s0962-8924(00)01834-1 10998601

30. Weber J, Polo S, Maspero E. HECT E3 Ligases: A Tale With Multiple Facets. Front Physiol. 2019;10: 370. doi: 10.3389/fphys.2019.00370 31001145

31. Rotin D, Kumar S. Physiological functions of the HECT family of ubiquitin ligases. Nat Rev Mol Cell Biol. 2009;10: 398–409. doi: 10.1038/nrm2690 19436320

32. Spratt DE, Walden H, Shaw GS. RBR E3 ubiquitin ligases: new structures, new insights, new questions. Biochem J. 2014;458: 421–437. doi: 10.1042/BJ20140006 24576094

33. Sluimer J, Distel B. Regulating the human HECT E3 ligases. Cell Mol Life Sci. 2018;75: 3121–3141. doi: 10.1007/s00018-018-2848-2 29858610

34. Metzger MB, Pruneda JN, Klevit RE, Weissman AM. RING-type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Biochim Biophys Acta. 2013;1843: 47–60. doi: 10.1016/j.bbamcr.2013.05.026 23747565

35. Deshaies RJ, Joazeiro CA. RING domain E3 ubiquitin ligases. Annu Rev Biochem. 2009;78: 399–434. doi: 10.1146/annurev.biochem.78.101807.093809 19489725

36. Finley D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu Rev Biochem. 2009;78: 477–513. doi: 10.1146/annurev.biochem.78.081507.101607 19489727

37. Thrower JS, Hoffman L, Rechsteiner M, Pickart CM. Recognition of the polyubiquitin proteolytic signal. EMBO J. 2000;19: 94–102. doi: 10.1093/emboj/19.1.94 10619848

38. Akutsu M, Dikic I, Bremm A. Ubiquitin chain diversity at a glance. J Cell Sci. 2016;129: 875–880. doi: 10.1242/jcs.183954 26906419

39. Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009;37: 937–953. doi: 10.1042/BST0370937 19754430

40. Chen ZJ, Sun LJ. Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell. 2009;33: 275–286. doi: 10.1016/j.molcel.2009.01.014 19217402

41. Kawadler H, Yang X. Lys63-linked polyubiquitin chains: linking more than just ubiquitin. Cancer Biol Ther. 2006;5: 1273–1274. doi: 10.4161/cbt.5.10.3289 16969079

42. Park SW, Han MG, Park C, Ju YR, Ahn BY, Ryou J. Hantaan virus nucleocapsid protein stimulates MDM2-dependent p53 degradation. J Gen Virol. 2013;94: 2424–2428. doi: 10.1099/vir.0.054312-0 23994832

43. Kainulainen M, Habjan M, Hubel P, Busch L, Lau S, Colinge J, et al. Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH. J Virol. 2014;88: 3464–3473. doi: 10.1128/JVI.02914-13 24403578

44. Kainulainen M, Lau S, Samuel CE, Hornung V, Weber F. NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR. J Virol. 2016;90: 6140–6147. doi: 10.1128/JVI.00016-16 27122577

45. van Knippenberg I, Carlton-Smith C, Elliott RM. The N-terminus of Bunyamwera orthobunyavirus NSs protein is essential for interferon antagonism. J Gen Virol. 2010;91: 2002–2006. doi: 10.1099/vir.0.021774-0 20427562

46. Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015;10: 845–858. doi: 10.1038/nprot.2015.053 25950237

47. Vosper JM, McDowel GS, Hindley CJ, Fiore-Heriche CS, Kucerova R, Horan I, Philpott A. Ubiquitylation on canonical and non-canonical sites targets the transcription factor neurogenin for ubiquitin-mediated proteolysis. J Biol Chem. 2009;284: 15458–15468 doi: 10.1074/jbc.M809366200 19336407

48. Kravtsova-Ivantsiv Y, Ciechanover A. Non-canonical ubiquitin-based signals for proteasomal degradation. J Cell Sci. 2012;125: 539–548 doi: 10.1242/jcs.093567 22389393

49. Viswanathan K, Früh K, DeFilippis V. Viral hijacking of the host ubiquitin system to evade interferon responses. Curr Opin Microbiol. 2010;13: 517–523. doi: 10.1016/j.mib.2010.05.012 20699190

50. Rahman MM, McFadden G. Modulation of NF-κB signalling by microbial pathogens. Nat Rev Microbiol. 2011;9: 291–306. doi: 10.1038/nrmicro2539 21383764

51. Lindner HA. Deubiquitination in virus infection. Virology. 2007;362: 245–256. doi: 10.1016/j.virol.2006.12.035 17291557

52. Maelfait J, Beyaert R. Emerging role of ubiquitination in antiviral RIG-I signaling. Microbiol Mol Biol Rev. 2012;76: 33–45. doi: 10.1128/MMBR.05012-11 22390971

53. Heaton SM, Borg NA, Dixit VM. Ubiquitin in the activation and attenuation of innate antiviral immunity. J Exp Med. 2016;213: 1–13. doi: 10.1084/jem.20151531 26712804

54. Zhu H, Zheng C, Xing J, Wang S, Li S, Lin R, et al. Varicella-zoster virus immediate-early protein ORF61 abrogates the IRF3-mediated innate immune response through degradation of activated IRF3. J Virol. 2011;85: 11079–11089. doi: 10.1128/JVI.05098-11 21835786

55. Lanfranca MP, Mostafa HH, Davido DJ. HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate Immunity. Cells. 2014;3: 438–454. doi: 10.3390/cells3020438 24852129

56. Zhang L, Villa NY, McFadden G. Interplay between poxviruses and the cellular ubiquitin/ubiquitin-like pathways. FEBS Lett. 2009;583: 607–614. doi: 10.1016/j.febslet.2009.01.023 19174161

57. Oshiumi H, Miyashita M, Matsumoto M, Seya T. A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses. PLoS Pathog. 2013;9: e1003533. doi: 10.1371/journal.ppat.1003533 23950712

58. Mudhasani R, Tran JP, Retterer C, Kota KP, Whitehouse CA, Bavari S. Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase. PLoS Pathog. 2016;12: e1005437. doi: 10.1371/journal.ppat.1005437 26837067

59. Koliopoulos MG, Lethier M, van der Veen AG, et al. Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition. Nat Commun. 2018;9: 1820. doi: 10.1038/s41467-018-04214-8 29739942

60. Rajsbaum R, Albrecht RA, Wang MK, Maharaj NP, Versteeg GA, Nistal-Villán E, et al. Species-specific inhibition of RIG-I ubiquitination and IFN induction by the influenza A virus NS1 protein. PLoS Pathog. 2012;8: e1003059. doi: 10.1371/journal.ppat.1003059 23209422

61. Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, et al. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe. 2006;5: 439–449.

62. Sánchez-Aparicio MT, Feinman LJ, García-Sastre A, Shaw ML. Paramyxovirus V Proteins Interact with the RIG-I/TRIM25 Regulatory Complex and Inhibit RIG-I Signaling. J Virol. 2018;92: e01960–17. doi: 10.1128/JVI.01960-17 29321315

63. Ding S, Mooney N, Li B, et al. Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex. PLoS Pathog. 2016;12: e1005929. doi: 10.1371/journal.ppat.1005929 27706223

64. Riley BE, Lougheed JC, Callaway K, Velasquez M, Brecht E, Nguyen L, et al. Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases. Nat Commun. 2013;4: 1982. doi: 10.1038/ncomms2982 23770887

65. Kingstone RE, Chen CA, Rose JK. Calcium phosphate transfection. In: Ausubel F, Brent R, Kingston R, Moore D, Seidman J, Smith J, Struhl K, editors. Curr Protoc Mol Biol. New York: 63; 2003. 1–9.

66. Yoneyama M, Suhara W, Fukuhara Y, Sato M, Ozato K, Fujita T. Autocrine amplification of type I interferon gene expression mediated by interferon stimulated gene factor 3 (ISGF3). J Biochem. 1996;120: 160–169. doi: 10.1093/oxfordjournals.jbchem.a021379 8864859

67. Valassina M, Soldateschi D, dal Maso GM, Santini L, Bianchi S, Valensin PE, Cusi MG. Diagnostic Potential of Toscana Virus N Protein Expressed in Escherichia coli. J Clin Microbiol. 1999;37: 1237.

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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