Ly49C-Dependent Control of MCMV Infection by NK Cells Is -Regulated by MHC Class I Molecules

English version České info

We previously identified a viral murine cytomegalovirus (MCMV) strain whose variant m157 immunoevasin can bind the inhibitory Ly49C NK cell receptor in addition to activating Ly49H receptor in B6 mice. Here we show that simultaneous engagement of the two receptors by m157 hampers NK cell activation. Most Ly49H+ NK cells lack Ly49C in B6 mice, as a result, NK cell population efficiently controls MCMV infection; however, the anti-viral response is reduced in transgenic mice where all NK cells express Ly49C. MHC I masks Ly49C through cis-interactions, which restricts its inhibitory function. Indeed, B6 Ly49C Tg, β2m ko mice, that are deficient for MHC I, are highly susceptible to low dose of MCMV. Our findings indicate that both the NK cell repertoire and MHC I molecules control susceptibility vs resistance to viral infections.

Vyšlo v časopise: Ly49C-Dependent Control of MCMV Infection by NK Cells Is -Regulated by MHC Class I Molecules. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004161
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004161

Souhrn

Zdroje

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

2. EidenschenkC, DunneJ, JouanguyE, FourlinnieC, GineauL, et al. (2006) A novel primary immunodeficiency with specific natural-killer cell deficiency maps to the centromeric region of chromosome 8. Am J Hum Genet 78: 721–727.

3. Alford CA, Britt WJ (1996) Cytomegalovirus; Fields BN, editor. New York: Raven Press. 629–660 p.

4. PyzikM, KielczewskaA, VidalSM (2008) NK cell receptors and their MHC class I ligands in host response to cytomegalovirus: insights from the mouse genome. Semin Immunol 20: 331–342.

5. VivierE, TomaselloE, BaratinM, WalzerT, UgoliniS (2008) Functions of natural killer cells. Nat Immunol 9: 503–510.

6. BrownMG, DokunAO, HeuselJW, SmithHR, BeckmanDL, et al. (2001) Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science 292: 934–937.

7. DanielsKA, DevoraG, LaiWC, O'DonnellCL, BennettM, et al. (2001) Murine cytomegalovirus is regulated by a discrete subset of natural killer cells reactive with monoclonal antibody to Ly49H. J Exp Med 194: 29–44.

8. LeeSH, GirardS, MacinaD, BusaM, ZaferA, et al. (2001) Susceptibility to mouse cytomegalovirus is associated with deletion of an activating natural killer cell receptor of the C-type lectin superfamily. Nat Genet 28: 42–45.

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

10. 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.

11. VoigtV, ForbesCA, TonkinJN, Degli-EspostiMA, SmithHR, et al. (2003) Murine cytomegalovirus m157 mutation and variation leads to immune evasion of natural killer cells. Proc Natl Acad Sci U S A 100: 13483–13488.

12. BoothTW, ScalzoAA, CarrelloC, LyonsPA, FarrellHE, et al. (1993) Molecular and biological characterization of new strains of murine cytomegalovirus isolated from wild mice. Arch Virol 132: 209–220.

13. 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.

14. BerryR, NgN, SaundersPM, VivianJP, LinJ, et al. (2013) Targeting of a natural killer cell receptor family by a viral immunoevasin. Nat Immunol 14: 699–705.

15. KimS, Poursine-LaurentJ, TruscottSM, LybargerL, SongYJ, et al. (2005) Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature 436: 709–713.

16. FernandezNC, TreinerE, VanceRE, JamiesonAM, LemieuxS, et al. (2005) A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules. Blood 105: 4416–4423.

17. OrrMT, MurphyWJ, LanierLL (2010) ‘Unlicensed’ natural killer cells dominate the response to cytomegalovirus infection. Nat Immunol 11: 321–327.

18. PignatelliS, Dal MonteP, RossiniG, LandiniMP (2004) Genetic polymorphisms among human cytomegalovirus (HCMV) wild-type strains. Rev Med Virol 14: 383–410.

19. ScalzoAA, BrownMG, ChuDT, HeuselJW, YokoyamaWM, et al. (1999) Development of intra-natural killer complex (NKC) recombinant and congenic mouse strains for mapping and functional analysis of NK cell regulatory loci. Immunogenetics 49: 238–241.

20. BrennanJ, LemieuxS, FreemanJD, MagerDL, TakeiF (1996) Heterogeneity among Ly-49C natural killer (NK) cells: characterization of highly related receptors with differing functions and expression patterns. J Exp Med 184: 2085–2090.

21. ScarpellinoL, OeschgerF, GuillaumeP, CoudertJD, LevyF, et al. (2007) Interactions of Ly49 Family Receptors with MHC Class I Ligands in trans and cis. J Immunol 178: 1277–1284.

22. DouceyMA, ScarpellinoL, ZimmerJ, GuillaumeP, LuescherIF, et al. (2004) Cis association of Ly49A with MHC class I restricts natural killer cell inhibition. Nat Immunol 5: 328–336.

23. KarreK, LjunggrenHG, PiontekG, KiesslingR (1986) Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319: 675–678.

24. SunJC, LanierLL (2008) Cutting edge: viral infection breaks NK cell tolerance to “missing self”. J Immunol 181: 7453–7457.

25. BrycesonYT, LongEO (2008) Line of attack: NK cell specificity and integration of signals. Curr Opin Immunol 20: 344–352.

26. AndrewsDM, ScalzoAA, YokoyamaWM, SmythMJ, Degli-EspostiMA (2003) Functional interactions between dendritic cells and NK cells during viral infection. Nat Immunol 4: 175–181.

27. Fodil-CornuN, LeeSH, BelangerS, MakrigiannisAP, BironCA, et al. (2008) Ly49h-deficient C57BL/6 mice: a new mouse cytomegalovirus-susceptible model remains resistant to unrelated pathogens controlled by the NK gene complex. J Immunol 181: 6394–6405.

28. HayakawaY, SmythMJ (2006) CD27 Dissects Mature NK Cells into Two Subsets with Distinct Responsiveness and Migratory Capacity. J Immunol 176: 1517–1524.

29. HengelH, ReuschU, GutermannA, ZieglerH, JonjicS, et al. (1999) Cytomegaloviral control of MHC class I function in the mouse. Immunol Rev 168: 167–176.

30. 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.

31. PyzikM, CharbonneauB, Gendron-PontbriandEM, BabicM, KrmpoticA, et al. (2011) Distinct MHC class I-dependent NK cell-activating receptors control cytomegalovirus infection in different mouse strains. J Exp Med 208: 1105–1117.

32. van DommelenSL, TabariasHA, SmythMJ, Degli-EspostiMA (2003) Activation of natural killer (NK) T cells during murine cytomegalovirus infection enhances the antiviral response mediated by NK cells. J Virol 77: 1877–1884.

33. HeldW, MariuzzaRA (2008) Cis interactions of immunoreceptors with MHC and non-MHC ligands. Nat Rev Immunol 8: 269–278.

34. VeilletteA, LatourS, DavidsonD (2002) Negative regulation of immunoreceptor signaling. Annu Rev Immunol 20: 669–707.

35. RadosevicK, van LeeuwenMT, Segers-NoltenIM, FigdorCG, de GroothBG, et al. (1994) Changes in actin organization during the cytotoxic process. Cytometry 15: 320–326.

36. KrzewskiK, ChenX, StromingerJL (2008) WIP is essential for lytic granule polarization and NK cell cytotoxicity. Proc Natl Acad Sci U S A 105: 2568–2573.

37. ScalzoAA, FitzgeraldNA, SimmonsA, La VistaAB, ShellamGR (1990) Cmv-1, a genetic locus that controls murine cytomegalovirus replication in the spleen. J Exp Med 171: 1469–1483.

38. BackJ, ChalifourA, ScarpellinoL, HeldW (2007) Stable masking by H-2Dd cis ligand limits Ly49A relocalization to the site of NK cell/target cell contact. Proc Natl Acad Sci U S A 104: 3978–3983.

39. ChalifourA, ScarpellinoL, BackJ, BrodinP, DevevreE, et al. (2009) A Role for cis Interaction between the Inhibitory Ly49A receptor and MHC class I for natural killer cell education. Immunity 30: 337–347.

40. StebbinsCC, WatzlC, BilladeauDD, LeibsonPJ, BurshtynDN, et al. (2003) Vav1 dephosphorylation by the tyrosine phosphatase SHP-1 as a mechanism for inhibition of cellular cytotoxicity. Mol Cell Biol 23: 6291–6299.

41. KleijnenMF, HuppaJB, LucinP, MukherjeeS, FarrellH, et al. (1997) A mouse cytomegalovirus glycoprotein, gp34, forms a complex with folded class I MHC molecules in the ER which is not retained but is transported to the cell surface. EMBO J 16: 685–694.

42. ReuschU, MuranyiW, LucinP, BurgertHG, HengelH, et al. (1999) A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation. EMBO J 18: 1081–1091.

43. ZieglerH, ThaleR, LucinP, MuranyiW, FlohrT, et al. (1997) A mouse cytomegalovirus glycoprotein retains MHC class I complexes in the ERGIC/cis-Golgi compartments. Immunity 6: 57–66.

44. LiNL, FuL, UchtenhagenH, AchourA, BurshtynDN (2013) Cis association of leukocyte Ig-like receptor 1 with MHC class I modulates accessibility to antibodies and HCMV UL18. Eur J Immunol 43: 1042–1052.

45. PircherH, MakTW, LangR, BallhausenW, RuediE, et al. (1989) T cell tolerance to Mlsa encoded antigens in T cell receptor V beta 8.1 chain transgenic mice. EMBO J 8: 719–727.

46. ChalmerJE, MackenzieJS, StanleyNF (1977) Resistance to murine cytomegalovirus linked to the major histocompatibility complex of the mouse. J Gen Virol 37: 107–114.

47. FarrellHE, ShellamGR (1989) Immunoblot analysis of the antibody response to murine cytomegalovirus in genetically resistant and susceptible mice. J Gen Virol 70(Pt 10): 2573–2586.

48. XuJ, LyonsPA, CarterMD, BoothTW, Davis-PoynterNJ, et al. (1996) Assessment of antigenicity and genetic variation of glycoprotein B of murine cytomegalovirus. J Gen Virol 77(Pt 1): 49–59.

49. WarmingS, CostantinoN, CourtDL, JenkinsNA, CopelandNG (2005) Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res 33: e36.

50. RedwoodAJ, MesserleM, HarveyNL, HardyCM, KoszinowskiUH, et al. (2005) Use of a murine cytomegalovirus K181-derived bacterial artificial chromosome as a vaccine vector for immunocontraception. J Virol 79: 2998–3008.

51. AlterG, MalenfantJM, AltfeldM (2004) CD107a as a functional marker for the identification of natural killer cell activity. J Immunol Methods 294: 15–22.

52. BrunnerKT, MauelJ, CerottiniJC, ChapuisB (1968) Quantitative assay of the lytic action of immune lymphoid cells on 51-Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs. Immunology 14: 181–196.