Intact Type I Interferon Production and IRF7 Function in Sooty Mangabeys

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In contrast to pathogenic HIV/SIV infections of humans and rhesus macaques (RMs), natural SIV infection of sooty mangabeys (SMs) is typically non-pathogenic despite high viremia. Several studies suggested that low immune activation and relative resistance of CD4+ central memory T-cells from virus infection are mechanisms that protect SMs from AIDS. In 2008 it was reported that plasmacytoid dendritic cells (pDCs) of SMs exhibit attenuated interferon-alpha (IFN-α) responses to TLR7/9 ligands in vitro, and that species-specific amino acid substitutions in SM Interferon Regulatory Factor-7 (IRF7) are responsible for this observation. Based on these findings, these authors proposed that “muted” IFN-α responses are responsible for the benign nature of SIV infection in SMs. However, other studies indicated that acutely SIV-infected SMs show robust IFN-α responses and marked upregulation of Interferon Stimulated Genes (ISGs). To investigate this apparent disparity, we first examined the role of the reported IRF7 amino acid substitutions in SMs. To this end, we sequenced all IRF7 exons in 16 breeders, and exons displaying variability (exons 2,3,5,6,7,8) in the remainder of the colony (177 animals). We found that the reported Ser-Gly substitution at position 191 was a sequencing error, and that several of the remaining substitutions represent only minor alleles. In addition, functional assays using recombinant SM IRF7 showed no defect in its ability to translocate in the nucleus and drive transcription from an IFN-α promoter. Furthermore, in vitro stimulation of SM peripheral blood mononuclear cells with either the TLR7 agonist CL097 or SIV_mac239 induced an 500–800-fold induction of IFN-α and IFN-β mRNA, and levels of IFN-α production by pDCs similar to those of RMs or humans. These data establish that IFN-α and IRF7 signaling in SMs are largely intact, with differences with RMs that are minor and unlikely to play any role in the AIDS resistance of SIV-infected SMs.

Vyšlo v časopise: Intact Type I Interferon Production and IRF7 Function in Sooty Mangabeys. PLoS Pathog 9(8): e32767. doi:10.1371/journal.ppat.1003597
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003597

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Zdroje

1. SilvestriG, SodoraDL, KoupRA, PaiardiniM, O'NeilSP, et al. (2003) Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity 18: 441–452.

2. KankiPJ, AlroyJ, EssexM (1985) Isolation of T-lymphotropic retrovirus related to HTLV-III/LAV from wild-caught African green monkeys. Science 230: 951–954.

3. ChahroudiA, BosingerSE, VanderfordTH, PaiardiniM, SilvestriG (2012) Natural SIV hosts: showing AIDS the door. Science 335: 1188–1193.

4. TheofilopoulosAN, BaccalaR, BeutlerB, KonoDH (2005) Type I interferons (alpha/beta) in immunity and autoimmunity. Annu Rev Immunol 23: 307–336.

5. IwasakiA (2012) Innate immune recognition of HIV-1. Immunity 37: 389–398.

6. DerSD, ZhouA, WilliamsBR, SilvermanRH (1998) Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci U S A 95: 15623–15628.

7. SchogginsJW, RiceCM (2011) Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol 1: 519–525.

8. HyrczaMD, KovacsC, LoutfyM, HalpennyR, HeislerL, et al. (2007) Distinct transcriptional profiles in ex vivo CD4+ and CD8+ T cells are established early in human immunodeficiency virus type 1 infection and are characterized by a chronic interferon response as well as extensive transcriptional changes in CD8+ T cells. J Virol 81: 3477–3486.

9. BosingerSE, HosiawaKA, CameronMJ, PersadD, RanL, et al. (2004) Gene expression profiling of host response in models of acute HIV infection. J Immunol 173: 6858–6863.

10. BosingerSE, LiQ, GordonSN, KlattNR, DuanL, et al. (2009) Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J Clin Invest 119: 3556–3572.

11. RotgerM, DalmauJ, RauchA, McLarenP, BosingerSE, et al. (2011) Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque. J Clin Invest 121: 2391–2400.

12. NeumannA, PolisM, RozenbergL, JacksonJ, ReitanoK, et al. (2007) Differential antiviral effect of PEG-interferon-alpha-2b on HIV and HCV in the treatment of HIV/HCV co-infected patients. AIDS 21: 1855–1865.

13. PillaiSK, Abdel-MohsenM, GuatelliJ, SkaskoM, MontoA, et al. (2012) Role of retroviral restriction factors in the interferon-alpha-mediated suppression of HIV-1 in vivo. Proc Natl Acad Sci U S A 109: 3035–3040.

14. VanderfordTH, SlichterC, RogersKA, LawsonBO, ObaedeR, et al. (2012) Treatment of SIV-infected sooty mangabeys with a type-I IFN agonist results in decreased virus replication without inducing hyperimmune activation. Blood 119: 5750–5757.

15. von SydowM, SonnerborgA, GainesH, StrannegardO (1991) Interferon-alpha and tumor necrosis factor-alpha in serum of patients in various stages of HIV-1 infection. AIDS Res Hum Retroviruses 7: 375–380.

16. HerbeuvalJP, ShearerGM (2007) HIV-1 immunopathogenesis: how good interferon turns bad. Clin Immunol 123: 121–128.

17. SedaghatAR, GermanJ, TeslovichTM, CofrancescoJJr, JieCC, et al. (2008) Chronic CD4+ T-cell activation and depletion in human immunodeficiency virus type 1 infection: type I interferon-mediated disruption of T-cell dynamics. J Virol 82: 1870–1883.

18. FernandezS, TanaskovicS, HelbigK, RajasuriarR, KramskiM, et al. (2011) CD4+ T-cell deficiency in HIV patients responding to antiretroviral therapy is associated with increased expression of interferon-stimulated genes in CD4+ T cells. J Infect Dis 204: 1927–1935.

19. MandlJN, BarryAP, VanderfordTH, KozyrN, ChavanR, et al. (2008) Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med 14: 1077–1087.

20. HondaK, TaniguchiT (2006) IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 6: 644–658.

21. HarrisLD, TabbB, SodoraDL, PaiardiniM, KlattNR, et al. (2010) Downregulation of robust acute type I interferon responses distinguishes nonpathogenic simian immunodeficiency virus (SIV) infection of natural hosts from pathogenic SIV infection of rhesus macaques. J Virol 84: 7886–7891.

22. MeythalerM, MartinotA, WangZ, PryputniewiczS, KashetaM, et al. (2009) Differential CD4+ T-lymphocyte apoptosis and bystander T-cell activation in rhesus macaques and sooty mangabeys during acute simian immunodeficiency virus infection. J Virol 83: 572–583.

23. AbecasisGR, AltshulerD, AutonA, BrooksLD, DurbinRM, et al. (2010) A map of human genome variation from population-scale sequencing. Nature 467: 1061–1073.

24. SumpterB, DunhamR, GordonS, EngramJ, HennessyM, et al. (2007) Correlates of preserved CD4(+) T cell homeostasis during natural, nonpathogenic simian immunodeficiency virus infection of sooty mangabeys: implications for AIDS pathogenesis. J Immunol 178: 1680–1691.

25. TaaffeJ, ChahroudiA, EngramJ, SumpterB, MeekerT, et al. (2010) A five-year longitudinal analysis of sooty mangabeys naturally infected with simian immunodeficiency virus reveals a slow but progressive decline in CD4+ T-cell count whose magnitude is not predicted by viral load or immune activation. J Virol 84: 5476–5484.

26. tenOeverBR, SharmaS, ZouW, SunQ, GrandvauxN, et al. (2004) Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity. J Virol 78: 10636–10649.

27. SharmaS, tenOeverBR, GrandvauxN, ZhouGP, LinR, et al. (2003) Triggering the interferon antiviral response through an IKK-related pathway. Science 300: 1148–1151.

28. LinR, MamaneY, HiscottJ (2000) Multiple regulatory domains control IRF-7 activity in response to virus infection. J Biol Chem 275: 34320–34327.

29. AuWC, MoorePA, LaFleurDW, TombalB, PithaPM (1998) Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon A genes. J Biol Chem 273: 29210–29217.

30. DaiJ, MegjugoracNJ, AmruteSB, Fitzgerald-BocarslyP (2004) Regulation of IFN regulatory factor-7 and IFN-alpha production by enveloped virus and lipopolysaccharide in human plasmacytoid dendritic cells. J Immunol 173: 1535–1548.

31. PaiardiniM, CervasiB, Reyes-AvilesE, MicciL, OrtizAM, et al. (2011) Low levels of SIV infection in sooty mangabey central memory CD(4)(+) T cells are associated with limited CCR5 expression. Nat Med 17: 830–836.

32. GordonSN, KlattNR, BosingerSE, BrenchleyJM, MilushJM, et al. (2007) Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys. J Immunol 179: 3026–3034.

33. EstesJD, GordonSN, ZengM, ChahroudiAM, DunhamRM, et al. (2008) Early resolution of acute immune activation and induction of PD-1 in SIV-infected sooty mangabeys distinguishes nonpathogenic from pathogenic infection in rhesus macaques. J Immunol 180: 6798–6807.

34. ChangJ, LindsayRJ, KulkarniS, LifsonJD, CarringtonM, et al. (2011) Polymorphisms in interferon regulatory factor 7 reduce interferon-alpha responses of plasmacytoid dendritic cells to HIV-1. AIDS 25: 715–717.

35. FuQ, ZhaoJ, QianX, WongJL, KaufmanKM, et al. (2011) Association of a functional IRF7 variant with systemic lupus erythematosus. Arthritis Rheum 63: 749–754.

36. KawasakiA, FurukawaH, KondoY, ItoS, HayashiT, et al. (2012) Association of PHRF1-IRF7 region polymorphism with clinical manifestations of systemic lupus erythematosus in a Japanese population. Lupus 21: 890–895.

37. KatoH, SatoS, YoneyamaM, YamamotoM, UematsuS, et al. (2005) Cell type-specific involvement of RIG-I in antiviral response. Immunity 23: 19–28.

38. HoshinoK, SugiyamaT, MatsumotoM, TanakaT, SaitoM, et al. (2006) IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9. Nature 440: 949–953.

39. KawaiT, SatoS, IshiiKJ, CobanC, HemmiH, et al. (2004) Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol 5: 1061–1068.

40. ZhaoT, YangL, SunQ, ArguelloM, BallardDW, et al. (2007) The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways. Nat Immunol 8: 592–600.

41. HeikenwalderM, PolymenidouM, JuntT, SigurdsonC, WagnerH, et al. (2004) Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nat Med 10: 187–192.

42. TaylorKE, MossmanKL (2013) Recent advances in understanding viral evasion of type I interferon. Immunology 138: 190–197.

43. LitvakV, RatushnyAV, LampanoAE, SchmitzF, HuangAC, et al. (2012) A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral responses. Nature 490: 421–425.

44. LeeMS, KimB, OhGT, KimYJ (2013) OASL1 inhibits translation of the type I interferon-regulating transcription factor IRF7. Nat Immunol 14: 346–355.

45. O'BrienM, ManchesO, SabadoRL, BarandaSJ, WangY, et al. (2011) Spatiotemporal trafficking of HIV in human plasmacytoid dendritic cells defines a persistently IFN-alpha-producing and partially matured phenotype. J Clin Invest 121: 1088–1101.

46. LedererS, FavreD, WaltersKA, ProllS, KanwarB, et al. (2009) Transcriptional profiling in pathogenic and non-pathogenic SIV infections reveals significant distinctions in kinetics and tissue compartmentalization. PLoS Pathog 5: e1000296.

47. JacquelinB, MayauV, TargatB, LiovatAS, KunkelD, et al. (2009) Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. J Clin Invest 119: 3544–3555.

48. Campillo-GimenezL, LaforgeM, FayM, BrusselA, CumontMC, et al. (2010) Nonpathogenesis of simian immunodeficiency virus infection is associated with reduced inflammation and recruitment of plasmacytoid dendritic cells to lymph nodes, not to lack of an interferon type I response, during the acute phase. J Virol 84: 1838–1846.

49. MandlJN, AkondyR, LawsonB, KozyrN, StapransSI, et al. (2011) Distinctive TLR7 signaling, type I IFN production, and attenuated innate and adaptive immune responses to yellow fever virus in a primate reservoir host. J Immunol 186: 6406–6416.

50. BrenchleyJM, SilvestriG, DouekDC (2010) Nonprogressive and progressive primate immunodeficiency lentivirus infections. Immunity 32: 737–742.

51. SchindlerM, MunchJ, KutschO, LiH, SantiagoML, et al. (2006) Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell 125: 1055–1067.

52. SchindlerM, SchmokelJ, SpechtA, LiH, MunchJ, et al. (2008) Inefficient Nef-mediated downmodulation of CD3 and MHC-I correlates with loss of CD4+T cells in natural SIV infection. PLoS Pathog 4: e1000107.

53. BrenchleyJM, VintonC, TabbB, HaoXP, ConnickE, et al. (2012) Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections. Blood 120: 4172–4181.

54. BrenchleyJM, PriceDA, SchackerTW, AsherTE, SilvestriG, et al. (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12: 1365–1371.

55. BrenchleyJM, PaiardiniM, KnoxKS, AsherAI, CervasiB, et al. (2008) Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 112: 2826–2835.

56. BeaumierCM, HarrisLD, GoldsteinS, KlattNR, WhittedS, et al. (2009) CD4 downregulation by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection. Nat Med 15: 879–885.

57. SundaravaradanV, SaleemR, MicciL, GasperMA, OrtizAM, et al. (2013) Multifunctional Double-negative T Cells in Sooty Mangabeys Mediate T-helper Functions Irrespective of SIV Infection. PLoS Pathog 9: e1003441.

58. MilushJM, MirKD, SundaravaradanV, GordonSN, EngramJ, et al. (2011) Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells. J Clin Invest 121: 1102–1110.

59. LamoreauxL, RoedererM, KoupR (2006) Intracellular cytokine optimization and standard operating procedure. Nat Protoc 1: 1507–1516.