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The Human Herpesvirus-7 (HHV-7) U21 Immunoevasin Subverts NK-Mediated Cytoxicity through Modulation of MICA and MICB


Herpesviruses have evolved numerous immune evasion strategies to facilitate establishment of lifelong persistent infections. Many herpesviruses encode gene products devoted to preventing viral antigen presentation as a means of escaping detection by cytotoxic T lymphocytes. The human herpesvirus-7 (HHV-7) U21 gene product, for example, is an immunoevasin that binds to class I major histocompatibility complex molecules and redirects them to the lysosomal compartment. Virus infection can also induce the upregulation of surface ligands that activate NK cells. Accordingly, the herpesviruses have evolved a diverse array of mechanisms to prevent NK cell engagement of NK-activating ligands on virus-infected cells. Here we demonstrate that the HHV-7 U21 gene product interferes with NK recognition. U21 can bind to the NK activating ligand ULBP1 and reroute it to the lysosomal compartment. In addition, U21 downregulates the surface expression of the NK activating ligands MICA and MICB, resulting in a reduction in NK-mediated cytotoxicity. These results suggest that this single viral protein may interfere both with CTL-mediated recognition through the downregulation of class I MHC molecules as well as NK-mediated recognition through downregulation of NK activating ligands.


Vyšlo v časopise: The Human Herpesvirus-7 (HHV-7) U21 Immunoevasin Subverts NK-Mediated Cytoxicity through Modulation of MICA and MICB. PLoS Pathog 7(11): e32767. doi:10.1371/journal.ppat.1002362
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002362

Souhrn

Herpesviruses have evolved numerous immune evasion strategies to facilitate establishment of lifelong persistent infections. Many herpesviruses encode gene products devoted to preventing viral antigen presentation as a means of escaping detection by cytotoxic T lymphocytes. The human herpesvirus-7 (HHV-7) U21 gene product, for example, is an immunoevasin that binds to class I major histocompatibility complex molecules and redirects them to the lysosomal compartment. Virus infection can also induce the upregulation of surface ligands that activate NK cells. Accordingly, the herpesviruses have evolved a diverse array of mechanisms to prevent NK cell engagement of NK-activating ligands on virus-infected cells. Here we demonstrate that the HHV-7 U21 gene product interferes with NK recognition. U21 can bind to the NK activating ligand ULBP1 and reroute it to the lysosomal compartment. In addition, U21 downregulates the surface expression of the NK activating ligands MICA and MICB, resulting in a reduction in NK-mediated cytotoxicity. These results suggest that this single viral protein may interfere both with CTL-mediated recognition through the downregulation of class I MHC molecules as well as NK-mediated recognition through downregulation of NK activating ligands.


Zdroje

1. Tanaka-TayaKKondoTMukaiTMiyoshiHYamamotoY 1996 Seroepidemiological study of human herpesvirus-6 and -7 in children of different ages and detection of these two viruses in throat swabs by polymerase chain reaction. J Med Virol 48 88 94

2. HansenTHBouvierM 2009 MHC class I antigen presentation: learning from viral evasion strategies. Nat Rev Immunol 9 503 513

3. PowersCDeFilippisVMalouliDFruhK 2008 Cytomegalovirus immune evasion. Curr Top Microbiol Immunol 325 333 359

4. YewdellJWHillAB 2002 Viral interference with antigen presentation. Nat Immunol 3 1019 1025

5. ChampsaurMLanierLL 2010 Effect of NKG2D ligand expression on host immune responses. Immunol Rev 235 267 285

6. BiassoniR 2009 Human natural killer receptors, co-receptors, and their ligands. Curr Protoc Immunol Chapter 14: Unit 14.10

7. LanierLL 2008 Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol 9 495 502

8. LanierLL 2008 Evolutionary struggles between NK cells and viruses. Nat Rev Immunol 8 259 268

9. LisnićVJKrmpotićAJonjićS 2010 Modulation of natural killer cell activity by viruses. Curr Opin Microbiol 13 530 539

10. JonjićSBabićMPolićBKrmpotićA 2008 Immune evasion of natural killer cells by viruses. Curr Opin Immunol 20 30 38

11. CosmanDMullbergJSutherlandCLChinWArmitageR 2001 ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 14 123 133

12. LiPMorrisDLWillcoxBESteinleASpiesT 2001 Complex structure of the activating immunoreceptor NKG2D and its MHC class I-like ligand MICA. Nat Immunol 2 443 451

13. LiPWillieSTBauerSMorrisDLSpiesT 1999 Crystal structure of the MHC class I homolog MIC-A, a gammadelta T cell ligand. Immunity 10 577 584

14. RadaevSRostroBBrooksAGColonnaMSunPD 2001 Conformational plasticity revealed by the cocrystal structure of NKG2D and its class I MHC-like ligand ULBP3. Immunity 15 1039 1049

15. DunnCChalupnyNJSutherlandCLDoschSSivakumarPV 2003 Human cytomegalovirus glycoprotein UL16 causes intracellular sequestration of NKG2D ligands, protecting against natural killer cell cytotoxicity. J Exp Med 197 1427 1439

16. WuJChalupnyNJManleyTJRiddellSRCosmanD 2003 Intracellular retention of the MHC class I-related chain B ligand of NKG2D by the human cytomegalovirus UL16 glycoprotein. J Immunol 170 4196 4200

17. EagleRATraherneJAHairJRJafferjiITrowsdaleJ 2009 ULBP6/RAET1L is an additional human NKG2D ligand. Eur J Immunol 39 3207 3216

18. RölleAMousavi-JaziMErikssonMOdebergJSoderberg-NauclerC 2003 Effects of human cytomegalovirus infection on ligands for the activating NKG2D receptor of NK cells: up-regulation of UL16-binding protein (ULBP)1 and ULBP2 is counteracted by the viral UL16 protein. J Immunol 171 902 908

19. AshiruOBennettNJBoyleLHThomasMTrowsdaleJ 2009 NKG2D ligand MICA is retained in the cis-Golgi apparatus by human cytomegalovirus protein UL142. J Virol 83 12345 12354

20. KrmpoticAHasanMLoewendorfASauligTHaleniusA 2005 NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m145. J Exp Med 201 211 220

21. KrmpotićABuschDHBubićIGebhardtFHengelH 2002 MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo. Nat Immunol 3 529 535

22. LodoenMOgasawaraKHamermanJAAraseHHouchinsJP 2003 NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules. J Exp Med 197 1245 1253

23. LodoenMBAbenesGUmamotoSHouchinsJPLiuF 2004 The cytomegalovirus m155 gene product subverts natural killer cell antiviral protection by disruption of H60-NKG2D interactions. J Exp Med 200 1075 1081

24. McSharryBPBurgertH-GOwenDPStantonRJProd'hommeV 2008 Adenovirus E3/19K promotes evasion of NK cell recognition by intracellular sequestration of the NKG2D ligands major histocompatibility complex class I chain-related proteins A and B. J Virol 82 4585 4594

25. ThomasMBonameJMFieldSNejentsevSSalioM 2008 Down-regulation of NKG2D and NKp80 ligands by Kaposi's sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity. Proc Natl Acad Sci USA 105 1656 1661

26. ThomasMWillsMLehnerPJ 2008 Natural killer cell evasion by an E3 ubiquitin ligase from Kaposi's sarcoma-associated herpesvirus. Biochem Soc Trans 36 459 463

27. NachmaniDStern-GinossarNSaridRMandelboimO 2009 Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell Host Microbe 5 376 385

28. MayNAGlossonNLHudsonAW 2010 HHV-7 U21 downregulates classical and non-classical class I MHC molecules from the cell surface. J Virol 84 3738 3751

29. BahramSBresnahanMGeraghtyDESpiesT 1994 A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci U S A 91 6259 6263

30. StephensHA 2001 MICA and MICB genes: can the enigma of their polymorphism be resolved? Trends Immunol 22 378 385

31. GlossonNLGonyoPMayNASchneiderCLRistowLC 2010 Insight into the mechanism of human herpesvirus 7 U21-mediated diversion of class I MHC molecules to lysosomes. J Biol Chem 285 37016 37029

32. HudsonAWHowleyPMPloeghHL 2001 A human herpesvirus 7 glycoprotein, U21, diverts major histocompatibility complex class I molecules to lysosomes. J Virol 75 12347 12358

33. GlossonNLHudsonAW 2007 Human herpesvirus-6A and -6B encode viral immunoevasins that downregulate class I MHC molecules. Virology 365 125 135

34. GrohVWuJYeeCSpiesT 2002 Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 419 734 738

35. SalihHRAntropiusHGiesekeFLutzSZKanzL 2003 Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Blood 102 1389 1396

36. SalihHRGoehlsdorfDSteinleA 2006 Release of MICB molecules by tumor cells: mechanism and soluble MICB in sera of cancer patients. Hum Immunol 67 188 195

37. BoutetPAguera-GonzalezSAtkinsonSPenningtonCJEdwardsDR 2009 Cutting edge: the metalloproteinase ADAM17/TNF-alpha-converting enzyme regulates proteolytic shedding of the MHC class I-related chain B protein. J Immunol 182 49 53

38. Aguera-GonzalezSBoutetPReyburnHTVales-GomezM 2009 Brief residence at the plasma membrane of the MHC class I-related chain B is due to clathrin-mediated cholesterol-dependent endocytosis and shedding. J Immunol 182 4800 4808

39. ChenXTrivediPPGeBKrzewskiKStromingerJL 2007 Many NK cell receptors activate ERK2 and JNK1 to trigger microtubule organizing center and granule polarization and cytotoxicity. Proc Natl Acad Sci U S A 104 6329 6334

40. KrzewskiKStromingerJL 2008 The killer's kiss: the many functions of NK cell immunological synapses. Curr Opin Cell Biol 20 597 605

41. MistryARO'CallaghanCA 2007 Regulation of ligands for the activating receptor NKG2D. Immunology 121 439 447

42. Vales-GomezMWinterhalterARoda-NavarroPZimmermannABoyleL 2006 The human cytomegalovirus glycoprotein UL16 traffics through the plasma membrane and the nuclear envelope. Cell Microbiol 8 581 590

43. WelteSASinzgerCLutzSZSingh-JasujaHSampaioKL 2003 Selective intracellular retention of virally induced NKG2D ligands by the human cytomegalovirus UL16 glycoprotein. Eur J Immunol 33 194 203

44. HansenSGPowersCJRichardsRVenturaABFordJC 2010 Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus. Science 328 102 106

45. ArapovicJLenacTAntulovRPolicBRuzsicsZ 2009 Differential susceptibility of RAE-1 isoforms to mouse cytomegalovirus. J Virol 83 8198 8207

46. CoxJHBenninkJRYewdellJW 1991 Retention of adenovirus E19 glycoprotein in the endoplasmic reticulum is essential to its ability to block antigen presentation. J Exp Med 174 1629 1637

47. SesterMKoebernickKOwenDAoMBrombergY 2010 Conserved amino acids within the adenovirus 2 E3/19K protein differentially affect downregulation of MHC class I and MICA/B proteins. J Immunol 184 255 267

48. MostoslavskyGFabianAJRooneySAltFWMulliganRC 2006 Complete correction of murine Artemis immunodeficiency by lentiviral vector-mediated gene transfer. Proc Natl Acad Sci U S A 103 16406 16411

49. BarnstableCJBodmerWFBrownGGalfreGMilsteinC 1978 Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell 14 9 20

50. StamNJSpitsHPloeghHL 1986 Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J Immunol 137 2299 2306

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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