The Murine Gammaherpesvirus Immediate-Early Rta Synergizes with IRF4, Targeting Expression of the Viral M1 Superantigen to Plasma Cells

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Through coevolution with their hosts, gammaherpesviruses have acquired unique genes that aid in infection of a particular host. Here we study the regulation of the MHV68 M1 gene, which encodes a protein that modulates the host immune response. Using a strategy that allowed us to identify MHV68 infected cells in mice, we have determined that M1 expression is largely limited to the antibody producing plasma cells. In addition, we show that M1 gene expression is regulated by both cellular and viral factors, which allow the virus to fine-tune gene expression in response to environmental signals. These findings provide insights into M1 function through a better understanding of how M1 expression is regulated.

Vyšlo v časopise: The Murine Gammaherpesvirus Immediate-Early Rta Synergizes with IRF4, Targeting Expression of the Viral M1 Superantigen to Plasma Cells. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004302
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004302

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1. ClambeyET, VirginHWt, SpeckSH (2000) Disruption of the murine gammaherpesvirus 68 M1 open reading frame leads to enhanced reactivation from latency. J Virol 74: 1973–1984.

2. EvansAG, MoserJM, KrugLT, PozharskayaV, MoraAL, et al. (2008) A gammaherpesvirus-secreted activator of Vbeta4+ CD8+ T cells regulates chronic infection and immunopathology. J Exp Med 205: 669–684.

3. TrippRA, Hamilton-EastonAM, CardinRD, NguyenP, BehmFG, et al. (1997) Pathogenesis of an infectious mononucleosis-like disease induced by a murine gamma-herpesvirus: role for a viral superantigen? J Exp Med 185: 1641–1650.

4. HardyCL, FlanoE, CardinRD, KimIJ, NguyenP, et al. (2001) Factors controlling levels of CD8+ T-cell lymphocytosis associated with murine gamma-herpesvirus infection. Viral Immunol 14: 391–402.

5. TibbettsSA, van DykLF, SpeckSH, VirginHWt (2002) Immune control of the number and reactivation phenotype of cells latently infected with a gammaherpesvirus. J Virol 76: 7125–7132.

6. SteedA, BuchT, WaismanA, VirginHWt (2007) Gamma interferon blocks gammaherpesvirus reactivation from latency in a cell type-specific manner. J Virol 81: 6134–6140.

7. SteedAL, BartonES, TibbettsSA, PopkinDL, LutzkeML, et al. (2006) Gamma interferon blocks gammaherpesvirus reactivation from latency. J Virol 80: 192–200.

8. FlanoE, HardyCL, KimIJ, FranklingC, CoppolaMA, et al. (2004) T cell reactivity during infectious mononucleosis and persistent gammaherpesvirus infection in mice. J Immunol 172: 3078–3085.

9. BrooksJW, Hamilton-EastonAM, ChristensenJP, CardinRD, HardyCL, et al. (1999) Requirement for CD40 ligand, CD4(+) T cells, and B cells in an infectious mononucleosis-like syndrome. J Virol 73: 9650–9654.

10. McClellanKB, GangappaS, SpeckSH, VirginHWt (2006) Antibody-independent control of gamma-herpesvirus latency via B cell induction of anti-viral T cell responses. PLoS Pathog 2: e58.

11. CoppolaMA, FlanoE, NguyenP, HardyCL, CardinRD, et al. (1999) Apparent MHC-independent stimulation of CD8+ T cells in vivo during latent murine gammaherpesvirus infection. J Immunol 163: 1481–1489.

12. KnappeA, HillerC, ThurauM, WittmannS, HofmannH, et al. (1997) The superantigen-homologous viral immediate-early gene ie14/vsag in herpesvirus saimiri-transformed human T cells. J Virol 71: 9124–9133.

13. SutkowskiN, PalkamaT, CiurliC, SekalyRP, Thorley-LawsonDA, et al. (1996) An Epstein-Barr virus-associated superantigen. J Exp Med 184: 971–980.

14. SutkowskiN, ConradB, Thorley-LawsonDA, HuberBT (2001) Epstein-Barr virus transactivates the human endogenous retrovirus HERV-K18 that encodes a superantigen. Immunity 15: 579–589.

15. SutkowskiN, ChenG, CalderonG, HuberBT (2004) Epstein-Barr virus latent membrane protein LMP-2A is sufficient for transactivation of the human endogenous retrovirus HERV-K18 superantigen. J Virol 78: 7852–7860.

16. AhnJW, PowellKL, KellamP, AlberDG (2002) Gammaherpesvirus lytic gene expression as characterized by DNA array. J Virol 76: 6244–6256.

17. EbrahimiB, DutiaBM, RobertsKL, Garcia-RamirezJJ, DickinsonP, et al. (2003) Transcriptome profile of murine gammaherpesvirus-68 lytic infection. J Gen Virol 84: 99–109.

18. JohnsonLS, WillertEK, VirginHW (2010) Redefining the genetics of murine gammaherpesvirus 68 via transcriptome-based annotation. Cell Host Microbe 7: 516–526.

19. SimasJP, SwannD, BowdenR, EfstathiouS (1999) Analysis of murine gammaherpesvirus-68 transcription during lytic and latent infection. J Gen Virol 80 (Pt 1) 75–82.

20. Martinez-GuzmanD, RickabaughT, WuTT, BrownH, ColeS, et al. (2003) Transcription program of murine gammaherpesvirus 68. J Virol 77: 10488–10503.

21. MarquesS, EfstathiouS, SmithKG, HauryM, SimasJP (2003) Selective gene expression of latent murine gammaherpesvirus 68 in B lymphocytes. J Virol 77: 7308–7318.

22. FlanoE, KimIJ, WoodlandDL, BlackmanMA (2002) Gamma-herpesvirus latency is preferentially maintained in splenic germinal center and memory B cells. J Exp Med 196: 1363–1372.

23. CollinsCM, BossJM, SpeckSH (2009) Identification of infected B-cell populations by using a recombinant murine gammaherpesvirus 68 expressing a fluorescent protein. J Virol 83: 6484–6493.

24. SimasJP, BowdenRJ, PaigeV, EfstathiouS (1998) Four tRNA-like sequences and a serpin homologue encoded by murine gammaherpesvirus 68 are dispensable for lytic replication in vitro and latency in vivo. J Gen Virol 79 (Pt 1) 149–153.

25. CollinsCM, SpeckSH (2012) Tracking murine gammaherpesvirus 68 infection of germinal center B cells in vivo. PLoS One 7: e33230.

26. CollinsCM, SpeckSH (2014) Expansion of murine gammaherpesvirus latently infected B cells requires T follicular help. PLoS Pathog 10: e1004106.

27. LiangX, CollinsCM, MendelJB, IwakoshiNN, SpeckSH (2009) Gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected B lymphocytes. PLoS Pathog 5: e1000677.

28. ForrestJC, SpeckSH (2008) Establishment of B-cell lines latently infected with reactivation-competent murine gammaherpesvirus 68 provides evidence for viral alteration of a DNA damage-signaling cascade. J Virol 82: 7688–7699.

29. KleinU, CasolaS, CattorettiG, ShenQ, LiaM, et al. (2006) Transcription factor IRF4 controls plasma cell differentiation and class-switch recombination. Nat Immunol 7: 773–782.

30. OchiaiK, Maienschein-ClineM, SimonettiG, ChenJ, RosenthalR, et al. (2013) Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4. Immunity 38: 918–929.

31. SciammasR, ShafferAL, SchatzJH, ZhaoH, StaudtLM, et al. (2006) Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation. Immunity 25: 225–236.

32. De SilvaNS, SimonettiG, HeiseN, KleinU (2012) The diverse roles of IRF4 in late germinal center B-cell differentiation. Immunol Rev 247: 73–92.

33. DriggersPH, EnnistDL, GleasonSL, MakWH, MarksMS, et al. (1990) An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes. Proc Natl Acad Sci U S A 87: 3743–3747.

34. LaichalkLL, Thorley-LawsonDA (2005) Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo. J Virol 79: 1296–1307.

35. CrawfordDH, AndoI (1986) EB virus induction is associated with B-cell maturation. Immunology 59: 405–409.

36. WilsonSJ, TsaoEH, WebbBL, YeH, Dalton-GriffinL, et al. (2007) X box binding protein XBP-1s transactivates the Kaposi's sarcoma-associated herpesvirus (KSHV) ORF50 promoter, linking plasma cell differentiation to KSHV reactivation from latency. J Virol 81: 13578–13586.

37. BhendePM, DickersonSJ, SunX, FengWH, KenneySC (2007) X-box-binding protein 1 activates lytic Epstein-Barr virus gene expression in combination with protein kinase D. J Virol 81: 7363–7370.

38. SunCC, Thorley-LawsonDA (2007) Plasma cell-specific transcription factor XBP-1s binds to and transactivates the Epstein-Barr virus BZLF1 promoter. J Virol 81: 13566–13577.

39. YuF, FengJ, HaradaJN, ChandaSK, KenneySC, et al. (2007) B cell terminal differentiation factor XBP-1 induces reactivation of Kaposi's sarcoma-associated herpesvirus. FEBS Lett 581: 3485–3488.

40. LiuS, PavlovaIV, VirginHWt, SpeckSH (2000) Characterization of gammaherpesvirus 68 gene 50 transcription. J Virol 74: 2029–2037.

41. PavlovaI, LinCY, SpeckSH (2005) Murine gammaherpesvirus 68 Rta-dependent activation of the gene 57 promoter. Virology 333: 169–179.

42. PalmeriD, CarrollKD, Gonzalez-LopezO, LukacDM (2011) Kaposi's sarcoma-associated herpesvirus Rta tetramers make high-affinity interactions with repetitive DNA elements in the Mta promoter to stimulate DNA binding of RBP-Jk/CSL. J Virol 85: 11901–11915.

43. CarrollKD, KhadimF, SpadavecchiaS, PalmeriD, LukacDM (2007) Direct interactions of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 ORF50/Rta protein with the cellular protein octamer-1 and DNA are critical for specifying transactivation of a delayed-early promoter and stimulating viral reactivation. J Virol 81: 8451–8467.

44. XiX, PerssonLM, O'BrienMW, MohrI, WilsonAC (2012) Cooperation between viral interferon regulatory factor 4 and RTA to activate a subset of Kaposi's sarcoma-associated herpesvirus lytic promoters. J Virol 86: 1021–1033.

45. GuitoJ, LukacDM (2012) KSHV Rta Promoter Specification and Viral Reactivation. Front Microbiol 3: 30.

46. WakemanBS, JohnsonLS, PadenCR, GrayKS, VirginHW, et al. (2014) Identification of Alternative Transcripts Encoding the Essential Murine Gammaherpesvirus Lytic Transactivator RTA. J Virol 88: 5474–5490.

47. WeckKE, BarkonML, YooLI, SpeckSH, VirginHI (1996) Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68. J Virol 70: 6775–6780.

48. BraatenDC, McClellanJS, MessaoudiI, TibbettsSA, McClellanKB, et al. (2006) Effective control of chronic gamma-herpesvirus infection by unconventional MHC Class Ia-independent CD8 T cells. PLoS Pathog 2: e37.

49. KrugLT, EvansAG, GarganoLM, PadenCR, SpeckSH (2013) The absence of M1 leads to increased establishment of murine gammaherpesvirus 68 latency in IgD-negative B cells. J Virol 87: 3597–3604.

50. RangaswamyUS, SpeckSH (2014) Murine Gammaherpesvirus M2 Protein Induction of IRF4 via the NFAT Pathway Leads to IL-10 Expression in B Cells. PLoS Pathog 10: e1003858.

51. JacobyMA, VirginHWt, SpeckSH (2002) Disruption of the M2 gene of murine gammaherpesvirus 68 alters splenic latency following intranasal, but not intraperitoneal, inoculation. J Virol 76: 1790–1801.

52. HerskowitzJH, JacobyMA, SpeckSH (2005) The murine gammaherpesvirus 68 M2 gene is required for efficient reactivation from latently infected B cells. J Virol 79: 2261–2273.

53. SiegelAM, HerskowitzJH, SpeckSH (2008) The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation. PLoS Pathog 4: e1000039.

54. VermaSC, RobertsonES (2003) Molecular biology and pathogenesis of Kaposi sarcoma-associated herpesvirus. FEMS Microbiol Lett 222: 155–163.

55. de OliveiraVL, AlmeidaSC, SoaresHR, ParkhouseRM (2013) Selective B-cell expression of the MHV-68 latency-associated M2 protein regulates T-dependent antibody response and inhibits apoptosis upon viral infection. J Gen Virol 94: 1613–1623.

56. VirginHWt, PrestiRM, LiXY, LiuC, SpeckSH (1999) Three distinct regions of the murine gammaherpesvirus 68 genome are transcriptionally active in latently infected mice. J Virol 73: 2321–2332.

57. KrugLT, MoserJM, DickersonSM, SpeckSH (2007) Inhibition of NF-kappaB activation in vivo impairs establishment of gammaherpesvirus latency. PLoS Pathog 3: e11.

58. KwonH, Thierry-MiegD, Thierry-MiegJ, KimHP, OhJ, et al. (2009) Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factors. Immunity 31: 941–952.