Inhibition of the TRAIL Death Receptor by CMV Reveals Its Importance in NK Cell-Mediated Antiviral Defense

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TRAIL death receptors regulate apoptosis and inflammation, and growing evidence suggests their importance in promoting antiviral defenses. Many viruses encode strategies to modulate signaling by TNF family cytokines in order to shape host defenses. Cytomegaloviruses encode many immune modulatory genes, many of which target the TNF family, highlighting their critical role in host antiviral immunity. Here we show that the mouse cytomegalovirus (MCMV) m166 protein restricts cell surface expression of the TRAIL death receptor in infected cells, thus protecting them from TRAIL mediated apoptosis. An MCMV mutant lacking m166 gene expression (MCMV-m166stop) is severely attenuated for replication in vivo, especially in the liver, where a population of immature natural killer (NK) cells resides that express very high levels of TRAIL. These TRAIL-expressing NK cells are critical for antiviral defense, as their depletion restores replication of MCMV-m166stop to wildtype levels. In addition, replication of MCMV-m166stop is normal in TRAIL-DR deficient mice, definitively demonstrating the importance for m166-mediated inhibition of this TNFR in promoting viral replication and subverting host innate defenses.

Vyšlo v časopise: Inhibition of the TRAIL Death Receptor by CMV Reveals Its Importance in NK Cell-Mediated Antiviral Defense. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004268
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004268

Souhrn

Zdroje

1. BenedictCA (2003) Viruses and the TNF-related cytokines, an evolving battle. Cytokine Growth Factor Rev 14: 349–357.

2. LeeM, LiuF (2005) Genetic analysis of cytomegalovirus by shuttle mutagenesis. Methods Mol Biol 292: 371–386.

3. YuD, SilvaMC, ShenkT (2003) Functional map of human cytomegalovirus AD169 defined by global mutational analysis. Proc Natl Acad Sci U S A 100: 12396–12401.

4. Stern-GinossarN, WeisburdB, MichalskiA, LeVT, HeinMY, et al. (2012) Decoding human cytomegalovirus. Science 338: 1088–1093.

5. Benedict CA, Crozat K, Degli-Esposti M, Dalod M (2013) Host Genetic Models in Cytomegalovirus Immunology. In: Reddehase MJ, editor. Cytomegaloviruses: From Molecular Pathogenesis to Intervention: Caister Academic Press.

6. CannonMJ, SchmidDS, HydeTB (2010) Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 20: 202–213.

7. GriffithsP, PlotkinS, MocarskiE, PassR, SchleissM, et al. (2013) Desirability and feasibility of a vaccine against cytomegalovirus. Vaccine 31 Suppl 2: B197–203.

8. BironCA, ByronKS, SullivanJL (1989) Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med 320: 1731–1735.

9. KuijpersTW, BaarsPA, DantinC, van den BurgM, van LierRA, et al. (2008) Human NK cells can control CMV infection in the absence of T cells. Blood 112: 914–915.

10. Lopez-VergesS, MilushJM, SchwartzBS, PandoMJ, JarjouraJ, et al. (2011) Expansion of a unique CD57(+)NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proc Natl Acad Sci U S A 108: 14725–14732.

11. WuZ, SinzgerC, FrascaroliG, ReichelJ, BayerC, et al. (2013) Human Cytomegalovirus-Induced NKG2Chi CD57hi Natural Killer Cells Are Effectors Dependent on Humoral Antiviral Immunity. J Virol 87: 7717–7725.

12. WilkinsonGW, TomasecP, StantonRJ, ArmstrongM, Prod'hommeV, et al. (2008) Modulation of natural killer cells by human cytomegalovirus. J Clin Virol 41: 206–212.

13. BabicM, KrmpoticA, JonjicS (2011) All is fair in virus-host interactions: NK cells and cytomegalovirus. Trends Mol Med 17: 677–685.

14. VidalSM, KhakooSI, BironCA (2011) Natural killer cell responses during viral infections: flexibility and conditioning of innate immunity by experience. Current opinion in virology 1: 497–512.

15. BironCA, NguyenKB, PienGC, CousensLP, Salazar-MatherTP (1999) Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17: 189–220.

16. AshkenaziA, DixitVM (1999) Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 11: 255–260.

17. SchneiderP, OlsonD, TardivelA, BrowningB, LugovskoyA, et al. (2003) Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Biol Chem 278: 5444–5454.

18. SatoK, HidaS, TakayanagiH, YokochiT, KayagakiN, et al. (2001) Antiviral response by natural killer cells through TRAIL gene induction by IFN-alpha/beta. Eur J Immunol 31: 3138–3146.

19. TakedaK, HayakawaY, SmythMJ, KayagakiN, YamaguchiN, et al. (2001) Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nat Med 7: 94–100.

20. SmythMJ, CretneyE, TakedaK, WiltroutRH, SedgerLM, et al. (2001) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis. The Journal of experimental medicine 193: 661–670.

21. FengX, YanJ, WangY, ZierathJR, NordenskjoldM, et al. (2010) The proteasome inhibitor bortezomib disrupts tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and natural killer (NK) cell killing of TRAIL receptor-positive multiple myeloma cells. Molecular immunology 47: 2388–2396.

22. BenedictCA, WareCF (2012) TRAIL: not just for tumors anymore? J Exp Med 209: 1903–1906.

23. CumminsN, BadleyA (2009) The TRAIL to viral pathogenesis: the good, the bad and the ugly. Curr Mol Med 9: 495–505.

24. DunnC, BrunettoM, ReynoldsG, ChristophidesT, KennedyPT, et al. (2007) Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. J Exp Med 204: 667–680.

25. HerbeuvalJP, BoassoA, GrivelJC, HardyAW, AndersonSA, et al. (2005) TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells. Blood 105: 2458–2464.

26. SmithW, TomasecP, AichelerR, LoewendorfA, NemcovicovaI, et al. (2013) Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses. Cell Host Microbe 13: 324–335.

27. Prod'hommeV, SugrueDM, StantonRJ, NomotoA, DaviesJ, et al. (2010) Human cytomegalovirus UL141 promotes efficient downregulation of the natural killer cell activating ligand CD112. J Gen Virol 91: 2034–2039.

28. TomasecP, WangEC, DavisonAJ, VojtesekB, ArmstrongM, et al. (2005) Downregulation of natural killer cell-activating ligand CD155 by human cytomegalovirus UL141. Nat Immunol 6: 181–188.

29. LoewendorfA, BenedictCA (2010) Modulation of host innate and adaptive immune defenses by cytomegalovirus: timing is everything. J Intern Med 267: 483–501.

30. MocarskiES, UptonJW, KaiserWJ (2012) Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways. Nat Rev Immunol 12: 79–88.

31. NemcovicovaI, BenedictCA, ZajoncDM (2013) Structure of human cytomegalovirus UL141 binding to TRAIL-R2 reveals novel, non-canonical death receptor interactions. PLoS Pathog 9: e1003224.

32. HasanM, KrmpoticA, RuzsicsZ, BubicI, LenacT, et al. (2005) Selective down-regulation of the NKG2D ligand H60 by mouse cytomegalovirus m155 glycoprotein. J Virol 79: 2920–2930.

33. Juranic LisnicV, Babic CacM, LisnicB, TrsanT, MefferdA, et al. (2013) Dual analysis of the murine cytomegalovirus and host cell transcriptomes reveal new aspects of the virus-host cell interface. PLoS Pathog 9: e1003611.

34. VermaS, BenedictCA (2011) Sources and signals regulating type I interferon production: lessons learned from cytomegalovirus. J Interferon Cytokine Res 31: 211–218.

35. VermaS, WangQ, ChodaczekG, BenedictCA (2013) Lymphoid-tissue stromal cells coordinate innate defense to cytomegalovirus. J Virol 87: 6201–6210.

36. LohJ, ChuDT, O'GuinAK, YokoyamaWM, VirginHWt (2005) Natural killer cells utilize both perforin and gamma interferon to regulate murine cytomegalovirus infection in the spleen and liver. J Virol 79: 661–667.

37. XieX, StadniskyMD, CoatsER, Ahmed RahimMM, LundgrenA, et al. (2010) MHC class I D(k) expression in hematopoietic and nonhematopoietic cells confers natural killer cell resistance to murine cytomegalovirus. Proceedings of the National Academy of Sciences of the United States of America 107: 8754–8759.

38. BabicM, PyzikM, ZafirovaB, MitrovicM, ButoracV, et al. (2010) Cytomegalovirus immunoevasin reveals the physiological role of “missing self” recognition in natural killer cell dependent virus control in vivo. J Exp Med 207: 2663–2673.

39. LodoenM, OgasawaraK, HamermanJA, AraseH, HouchinsJP, et al. (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.

40. TakedaK, CretneyE, HayakawaY, OtaT, AkibaH, et al. (2005) TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver. Blood 105: 2082–2089.

41. ChiossoneL, ChaixJ, FuseriN, RothC, VivierE, et al. (2009) Maturation of mouse NK cells is a 4-stage developmental program. Blood 113: 5488–5496.

42. McGeochDJ, DolanA, RalphAC (2000) Toward a comprehensive phylogeny for mammalian and avian herpesviruses. J Virol 74: 10401–10406.

43. YoshidaT, ShiraishiT, NakataS, HorinakaM, WakadaM, et al. (2005) Proteasome inhibitor MG132 induces death receptor 5 through CCAAT/enhancer-binding protein homologous protein. Cancer research 65: 5662–5667.

44. ZhuJ, ChenJ, HaiR, TongT, XiaoJ, et al. (2003) In vitro and in vivo characterization of a murine cytomegalovirus with a mutation at open reading frame m166. J Virol 77: 2882–2891.

45. JonjicS, PolicB, KrmpoticA (2008) Viral inhibitors of NKG2D ligands: friends or foes of immune surveillance? Eur J Immunol 38: 2952–2956.

46. HandkeW, KrauseE, BruneW (2012) Live or let die: manipulation of cellular suicide programs by murine cytomegalovirus. Med Microbiol Immunol 201: 475–486.

47. ZamaiL, AhmadM, BennettIM, AzzoniL, AlnemriES, et al. (1998) Natural killer (NK) cell-mediated cytotoxicity: differential use of TRAIL and Fas ligand by immature and mature primary human NK cells. J Exp Med 188: 2375–2380.

48. AraseH, MocarskiES, CampbellAE, HillAB, LanierLL (2002) Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296: 1323–1326.

49. SmithHR, HeuselJW, MehtaIK, KimS, DornerBG, et al. (2002) Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci U S A 99: 8826–8831.

50. CorbettAJ, CoudertJD, ForbesCA, ScalzoAA (2011) Functional consequences of natural sequence variation of murine cytomegalovirus m157 for Ly49 receptor specificity and NK cell activation. J Immunol 186: 1713–1722.

51. DiehlGE, YueHH, HsiehK, KuangAA, HoM, et al. (2004) TRAIL-R as a negative regulator of innate immune cell responses. Immunity 21: 877–889.

52. StaceyMA, MarsdenM, PhamNTA, ClareS, DoltonG, et al. (2014) Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV. Cell Host Microbe 15: 471–83.

53. PoliA, MichelT, TheresineM, AndresE, HentgesF, et al. (2009) CD56bright natural killer (NK) cells: an important NK cell subset. Immunology 126: 458–465.

54. AndrewsJI, GriffithTS, MeierJL (2007) Cytomegalovirus and the role of interferon in the expression of tumor necrosis factor-related apoptosis-inducing ligand in the placenta. American journal of obstetrics and gynecology 197: 608 e601–606.

55. TischerBK, SmithGA, OsterriederN (2010) En passant mutagenesis: a two step markerless red recombination system. Methods Mol Biol 634: 421–430.

56. MesserleM, CrnkovicI, HammerschmidtW, ZieglerH, KoszinowskiUH (1997) Cloning and mutagenesis of a herpesvirus genome as an infectious bacterial artificial chromosome. Proc Natl Acad Sci U S A 94: 14759–14763.

57. SchneiderK, LoewendorfA, De TrezC, FultonJ, RhodeA, et al. (2008) Lymphotoxin-mediated crosstalk between B cells and splenic stroma promotes the initial type I interferon response to cytomegalovirus. Cell Host Microbe 3: 67–76.