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A Gammaherpesvirus Bcl-2 Ortholog Blocks B Cell Receptor-Mediated Apoptosis and Promotes the Survival of Developing B Cells


Gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8) establish lifelong latency in their hosts and are associated with the development of several types of malignancies, including a subset of B cell lymphomas. These viruses are thought to co-opt the process of B cell differentiation to latently infect a fraction of circulating memory B cells, resulting in the establishment of a stable latency setpoint. However, little is known about how this infected memory B cell compartment is maintained throughout the life of the host. We have previously demonstrated that immature and transitional B cells are long-term latency reservoirs for murine gammaherpesvirus 68 (MHV68), suggesting that infection of developing B cells contributes to the maintenance of lifelong latency. During hematopoiesis, immature and transitional B cells are subject to B cell receptor (BCR)-mediated negative selection, which results in the clonal deletion of autoreactive B cells. Interestingly, numerous gammaherpesviruses encode homologs of the anti-apoptotic protein Bcl-2, suggesting that virus inhibition of apoptosis could subvert clonal deletion. To test this, we quantified latency establishment in mice inoculated with MHV68 vBcl-2 mutants. vBcl-2 mutant viruses displayed a marked decrease in the frequency of immature and transitional B cells harboring viral genome, but this attenuation could be rescued by increased host Bcl-2 expression. Conversely, vBcl-2 mutant virus latency in early B cells and mature B cells, which are not targets of negative selection, was remarkably similar to wild-type virus. Finally, in vivo depletion of developing B cells during chronic infection resulted in decreased mature B cell latency, demonstrating a key role for developing B cells in the maintenance of lifelong latency. Collectively, these findings support a model in which gammaherpesvirus latency in circulating mature B cells is sustained in part through the recurrent infection and vBcl-2-mediated survival of developing B cells.


Vyšlo v časopise: A Gammaherpesvirus Bcl-2 Ortholog Blocks B Cell Receptor-Mediated Apoptosis and Promotes the Survival of Developing B Cells. PLoS Pathog 10(2): e32767. doi:10.1371/journal.ppat.1003916
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003916

Souhrn

Gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8) establish lifelong latency in their hosts and are associated with the development of several types of malignancies, including a subset of B cell lymphomas. These viruses are thought to co-opt the process of B cell differentiation to latently infect a fraction of circulating memory B cells, resulting in the establishment of a stable latency setpoint. However, little is known about how this infected memory B cell compartment is maintained throughout the life of the host. We have previously demonstrated that immature and transitional B cells are long-term latency reservoirs for murine gammaherpesvirus 68 (MHV68), suggesting that infection of developing B cells contributes to the maintenance of lifelong latency. During hematopoiesis, immature and transitional B cells are subject to B cell receptor (BCR)-mediated negative selection, which results in the clonal deletion of autoreactive B cells. Interestingly, numerous gammaherpesviruses encode homologs of the anti-apoptotic protein Bcl-2, suggesting that virus inhibition of apoptosis could subvert clonal deletion. To test this, we quantified latency establishment in mice inoculated with MHV68 vBcl-2 mutants. vBcl-2 mutant viruses displayed a marked decrease in the frequency of immature and transitional B cells harboring viral genome, but this attenuation could be rescued by increased host Bcl-2 expression. Conversely, vBcl-2 mutant virus latency in early B cells and mature B cells, which are not targets of negative selection, was remarkably similar to wild-type virus. Finally, in vivo depletion of developing B cells during chronic infection resulted in decreased mature B cell latency, demonstrating a key role for developing B cells in the maintenance of lifelong latency. Collectively, these findings support a model in which gammaherpesvirus latency in circulating mature B cells is sustained in part through the recurrent infection and vBcl-2-mediated survival of developing B cells.


Zdroje

1. Sunil-ChandraNP, ArnoJ, FazakerleyJ, NashAA (1994) Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68. Am J Pathol 145: 818–826.

2. TarakanovaVL, SuarezF, TibbettsSA, JacobyMA, WeckKE, et al. (2005) Murine Gammaherpesvirus 68 Infection Is Associated with Lymphoproliferative Disease and Lymphoma in BALB {beta}2 Microglobulin-Deficient Mice. J Virol 79: 14668–14679 doi:10.1128/JVI.79.23.14668-14679.2005

3. CesarmanE (2011) Gammaherpesvirus and lymphoproliferative disorders in immunocompromised patients. Spec Issue Infect Hum Cancer 305: 163–174 doi:10.1016/j.canlet.2011.03.003

4. Thorley-LawsonDA, GrossA (2004) Persistence of the Epstein-Barr Virus and the Origins of Associated Lymphomas. N Engl J Med 350: 1328–1337 doi:10.1056/NEJMra032015

5. KhanG, MiyashitaEM, YangB, BabcockGJ, Thorley-LawsonDA (1996) Is EBV persistence in vivo a model for B cell homeostasis? Immunity 5: 173–179.

6. FlanoE, KimI-J, WoodlandDL, BlackmanMA (2002) {gamma}-Herpesvirus Latency Is Preferentially Maintained in Splenic Germinal Center and Memory B Cells. J Exp Med 196: 1363–1372 doi:10.1084/jem.20020890

7. WillerDO, SpeckSH (2003) Long-Term Latent Murine Gammaherpesvirus 68 Infection Is Preferentially Found within the Surface Immunoglobulin D-Negative Subset of Splenic B Cells In Vivo. J Virol 77: 8310–8321 doi:10.1128/JVI.77.15.8310-8321.2003

8. NealyMS, ColemanCB, LiH, TibbettsSA (2010) Use of a Virus-Encoded Enzymatic Marker Reveals that a Stable Fraction of Memory B Cells Expresses Latency-Associated Nuclear Antigen throughout Chronic Gammaherpesvirus Infection. J Virol 84: 7523–7534 doi:10.1128/JVI.02572-09

9. Thorley-LawsonDA (2001) Epstein-Barr virus: exploiting the immune system. Nat Rev Immunol 1: 75–82 doi:10.1038/35095584

10. Thorley-LawsonDA, BabcockGJ (1999) A model for persistent infection with Epstein-Barr virus: The stealth virus of human B cells. Life Sci 65: 1433–1453 doi:10.1016/S0024-3205(99)00214-3

11. 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 doi:10.1128/JVI.00297-09

12. MarquesS, EfstathiouS, SmithKG, HauryM, SimasJP (2003) Selective Gene Expression of Latent Murine Gammaherpesvirus 68 in B Lymphocytes. J Virol 77: 7308–7318 doi:10.1128/JVI.77.13.7308-7318.2003

13. ColemanCB, NealyMS, TibbettsSA (2010) Immature and transitional B cells are latency reservoirs for a gammaherpesvirus. J Virol 84: 13045–13052 doi:10.1128/JVI.01455-10

14. AllmanDM, FergusonSE, LentzVM, CancroMP (1993) Peripheral B cell maturation. II. Heat-stable antigen(hi) splenic B cells are an immature developmental intermediate in the production of long-lived marrow-derived B cells. J Immunol Baltim Md 1950 151: 4431–4444.

15. AllmanD, LindsleyRC, DeMuthW, RuddK, ShintonSA, et al. (2001) Resolution of Three Nonproliferative Immature Splenic B Cell Subsets Reveals Multiple Selection Points During Peripheral B Cell Maturation. J Immunol 167: 6834–6840.

16. RolinkAG, ten BoekelE, YamagamiT, CeredigR, AnderssonJ, et al. (1999) B cell development in the mouse from early progenitors to mature B cells. Immunol Lett 68: 89–93 doi:10.1016/S0165-2478(99)00035-8

17. HardyRR, HayakawaK (2001) B CELL DEVELOPMENT PATHWAYS. Annu Rev Immunol 19: 595–621 doi:10.1146/annurev.immunol.19.1.595

18. ChungJB, SilvermanM, MonroeJG (2003) Transitional B cells: step by step towards immune competence. Trends Immunol 24: 342–348 doi:10.1016/S1471-4906(03)00119-4

19. PelandaR, TorresRM (2006) Receptor editing for better or for worse. Lymph Dev Tumour Immunol 18: 184–190 doi:10.1016/j.coi.2006.01.005

20. GauldSB, MerrellKT, CambierJC (2006) Silencing of autoreactive B cells by anergy: a fresh perspective. Lymph Act Lymph Eff Funct 18: 292–297 doi:10.1016/j.coi.2006.03.015

21. KingL, MonroeJ (2000) Immunobiology of the immature B cell: plasticity in the B-cell antigen receptor-induced response fine tunes negative selection. Immunol Rev 176: 86–104 doi:10.1034/j.1600-065X.2000.00609.x

22. HippenKL, SchramBR, TzeLE, PapeKA, JenkinsMK, et al. (2005) In Vivo Assessment of the Relative Contributions of Deletion, Anergy, and Editing to B Cell Self-Tolerance. J Immunol 175: 909–916.

23. SandelPC, MonroeJG (1999) Negative Selection of Immature B Cells by Receptor Editing or Deletion Is Determined by Site of Antigen Encounter. Immunity 10: 289–299 doi:10.1016/S1074-7613(00)80029-1

24. WangH, FengJ, QiC-F, LiZ, MorseHC, et al. (2007) Transitional B Cells Lose Their Ability to Receptor Edit but Retain Their Potential for Positive and Negative Selection. J Immunol 179: 7544–7552.

25. HartleySB, CookeMP, FulcherDA, HarrisAW, CoryS, et al. (1993) Elimination of self-reactive B lymphocytes proceeds in two stages: Arrested development and cell death. Cell 72: 325–335 doi:10.1016/0092-8674(93)90111-3

26. NiiroH, ClarkEA (2002) Regulation of B-cell fate by antigen-receptor signals. Nat Rev Immunol 2: 945–956 doi:10.1038/nri955

27. CarsettiR, KöhlerG, LamersMC (1995) Transitional B cells are the target of negative selection in the B cell compartment. J Exp Med 181: 2129–2140 doi:10.1084/jem.181.6.2129

28. MerinoR, DingL, VeisDJ, KorsmeyerSJ, NuñezG (1994) Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes. Embo J 13: 683–691.

29. SuTT, GuoB, KawakamiY, SommerK, ChaeK, et al. (2002) PKC-β controls IκB kinase lipid raft recruitment and activation in response to BCR signaling. Nat Immunol 3: 780–786 doi:10.1038/ni823

30. SuTT, RawlingsDJ (2002) Transitional B Lymphocyte Subsets Operate as Distinct Checkpoints in Murine Splenic B Cell Development. J Immunol 168: 2101–2110.

31. TomaykoMM, CancroMP (1998) Long-Lived B Cells Are Distinguished by Elevated Expression of A1. J Immunol 160: 107–111.

32. StrasserA, WhittinghamS, VauxDL, BathML, AdamsJM, et al. (1991) Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci 88: 8661–8665.

33. LangJ, ArnoldB, HammerlingG, HarrisAW, KorsmeyerS, et al. (1997) Enforced Bcl-2 Expression Inhibits Antigen-mediated Clonal Elimination of Peripheral B Cells in an Antigen Dose–dependent Manner and Promotes Receptor Editing in Autoreactive, Immature B Cells. J Exp Med 186: 1513–1522 doi:10.1084/jem.186.9.1513

34. FangW, WeintraubBC, DunlapB, GarsideP, PapeKA, et al. (1998) Self-Reactive B Lymphocytes Overexpressing Bcl-xL Escape Negative Selection and Are Tolerized by Clonal Anergy and Receptor Editing. Immunity 9: 35–45 doi:10.1016/S1074-7613(00)80586-5

35. HendersonS, HuenD, RoweM, DawsonC, JohnsonG, et al. (1993) Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc Natl Acad Sci 90: 8479–8483.

36. ChengEH-Y, NicholasJ, BellowsDS, HaywardGS, GuoH-G, et al. (1997) A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc Natl Acad Sci 94: 690–694.

37. MarshallWL, YimC, GustafsonE, GrafT, SageDR, et al. (1999) Epstein-Barr Virus Encodes a Novel Homolog of the bcl-2 Oncogene That Inhibits Apoptosis and Associates with Bax and Bak. J Virol 73: 5181–5185.

38. ThomeM, SchneiderP, HofmannK, FickenscherH, MeinlE, et al. (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386: 517–521 doi:10.1038/386517a0

39. FanidiA, HancockDC, LittlewoodTD (1998) Suppression of c-Myc-Induced Apoptosis by the Epstein-Barr Virus Gene Product BHRF1. J Virol 72: 8392–8395.

40. VirginHW, LatreilleP, WamsleyP, HallsworthK, WeckKE, et al. (1997) Complete sequence and genomic analysis of murine gammaherpesvirus 68. J Virol 71: 5894–5904.

41. WangG-H, GarveyTL, CohenJI (1999) The murine gammaherpesvirus-68 M11 protein inhibits Fas- and TNF- induced apoptosis. J Gen Virol 80: 2737–2740.

42. VirginHW, PrestiRM, LiX-Y, LiuC, SpeckSH (1999) Three Distinct Regions of the Murine Gammaherpesvirus 68 Genome Are Transcriptionally Active in Latently Infected Mice. J Virol 73: 2321–2332.

43. LohJ, HuangQ, PetrosAM, NettesheimD, van DykLF, et al. (2005) A Surface Groove Essential for Viral Bcl-2 Function During Chronic Infection In Vivo. Plos Pathog 1: e10 doi:10.1371/journal.ppat.0010010

44. RoyDJ, EbrahimiBC, DutiaBM, NashAA, StewartJP (2000) Murine gammaherpesvirus M11 gene product inhibits apoptosis and is expressed during virus persistence. Arch Virol 145: 2411–2420 doi:10.1007/s007050070030

45. BellowsDS, ChauBN, LeeP, LazebnikY, BurnsWH, et al. (2000) Antiapoptotic Herpesvirus Bcl-2 Homologs Escape Caspase-Mediated Conversion to Proapoptotic Proteins. J Virol 74: 5024–5031 doi:10.1128/JVI.74.11.5024-5031.2000

46. SinhaSC, ColbertCL, BeckerN, WeiY, LevineB (2008) Molecular basis of the regulation of Beclin 1-dependent autophagy by the γ-herpesvirus 68 Bcl-2 homolog M11. Autophagy 4: 989–997.

47. KuB, WooJ-S, LiangC, LeeK-H, HongH-S, et al. (2008) Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine γ-Herpesvirus 68. Plos Pathog 4: e25 doi:10.1371/journal.ppat.0040025

48. De LimaBD, MayJS, MarquesS, SimasJP, StevensonPG (2005) Murine gammaherpesvirus 68 bcl-2 homologue contributes to latency establishment in vivo. J Gen Virol 86: 31–40 doi:10.1099/vir.0.80480-0

49. EX, HwangS, OhS, LeeJ-S, JeongJH, et al. (2009) Viral Bcl-2-Mediated Evasion of Autophagy Aids Chronic Infection of γHerpesvirus 68. Plos Pathog 5: e1000609 doi:10.1371/journal.ppat.1000609

50. GangappaS, van DykLF, JewettTJ, SpeckSH, VirginHW (2002) Identification of the In Vivo Role of a Viral bcl-2. J Exp Med 195: 931–940 doi:10.1084/jem.20011825

51. LoderF, MutschlerB, RayRJ, PaigeCJ, SiderasP, et al. (1999) B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals. J Exp Med 190: 75–89.

52. TibbettsSA, van DykLF, SpeckSH, VirginHW (2002) Immune Control of the Number and Reactivation Phenotype of Cells Latently Infected with a Gammaherpesvirus. J Virol 76: 7125–7132 doi:10.1128/JVI.76.14.7125-7132.2002

53. WeckKE, KimSS, VirginHW, SpeckSH (1999) B Cells Regulate Murine Gammaherpesvirus 68 Latency. J Virol 73: 4651–4661.

54. Van DykLF, VirginHW, SpeckSH (2000) The Murine Gammaherpesvirus 68 v-Cyclin Is a Critical Regulator of Reactivation from Latency. J Virol 74: 7451–7461 doi:10.1128/JVI.74.16.7451-7461.2000

55. RoyV, ChangN-H, CaiY, BonventiG, WitherJ (2005) Aberrant IgM Signaling Promotes Survival of Transitional T1 B Cells and Prevents Tolerance Induction in Lupus-Prone New Zealand Black Mice. J Immunol 175: 7363–7371.

56. KozonoY, KotzinBL, HolersVM (1996) Resting B cells from New Zealand Black mice demonstrate a defect in apoptosis induction following surface IgM ligation. J Immunol 156: 4498–4503.

57. LarsonJD, ThurmanJM, RubtsovAV, ClaypoolD, MarrackP, et al. (2012) Murine gammaherpesvirus 68 infection protects lupus-prone mice from the development of autoimmunity. Proc Natl Acad Sci 109: E1092–E1100 doi:10.1073/pnas.1203019109

58. HasboldJ, KlausGGB (1990) Anti-immunoglobulin antibodies induce apoptosis in immature B cell lymphomas. Eur J Immunol 20: 1685–1690 doi:10.1002/eji.1830200810

59. BenhamouLE, CazenaveP, SarthouP (1990) Anti-immunoglobulins induce death by apoptosis in WEHI-231 B lymphoma cells. Eur J Immunol 20: 1405–1407 doi:10.1002/eji.1830200630

60. CherrySR, BiniszkiewiczD, van ParijsL, BaltimoreD, JaenischR (2000) Retroviral expression in embryonic stem cells and hematopoietic stem cells. Mol Cell Biol 20: 7419–7426.

61. LieuFH, HawleyTS, FongAZ, HawleyRG (1997) Transmissibility of murine stem cell virus-based retroviral vectors carrying both interleukin-12 cDNAs and a third gene: implications for immune gene therapy. Cancer Gene Ther 4: 167–175.

62. SuzukiS, ChuangLF, DoiRH, ChuangRY (2003) Morphine suppresses lymphocyte apoptosis by blocking p53-mediated death signaling. Biochem Biophys Res Commun 308: 802–808 doi:10.1016/S0006-291X(03)01472-4

63. KasaiT, OhguchiK, NakashimaS, ItoY, NaganawaT, et al. (1998) Increased Activity of Oleate-Dependent Type Phospholipase D During Actinomycin D-Induced Apoptosis in Jurkat T Cells. J Immunol 161: 6469–6474.

64. ChoongML, YangH, LeeMA, LaneDP (2009) Specific activation of the p53 pathway by low dose actinomycin D: A new route to p53 based cyclotherapy. Cell Cycle 8: 2810–2818.

65. ShimD, KangHY, JeonBW, KangSS, ChangS-I, et al. (2004) Protein kinase B inhibits apoptosis induced by actinomycin D in ECV304 cells through phosphorylation of caspase 8. Arch Biochem Biophys 425: 214–220 doi:10.1016/j.abb.2004.03.028

66. GrabsteinKH, WaldschmidtTJ, FinkelmanFD, HessBW, AlpertAR, et al. (1993) Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody. J Exp Med 178: 257–264 doi:10.1084/jem.178.1.257

67. MilneCD, FlemingHE, ZhangY, PaigeCJ (2004) Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin-1 during B-cell development. Immunol Rev 197: 75–88 doi:10.1111/j.0105-2896.2004.0103.x

68. EricksonLD, TygrettLT, BhatiaSK, GrabsteinKH, WaldschmidtTJ (1996) Differential expression of CD22 (Lyb8) on murine B cells. Int Immunol 8: 1121–1129 doi:10.1093/intimm/8.7.1121

69. EhtishamS, Sunil-ChandraNP, NashAA (1993) Pathogenesis of murine gammaherpesvirus infection in mice deficient in CD4 and CD8 T cells. J Virol 67: 5247–5252.

70. CardinRD, BrooksJW, SarawarSR, DohertyPC (1996) Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells. J Exp Med 184: 863–871.

71. FlañoE, WoodlandDL, BlackmanMA (1999) Requirement for CD4+ T Cells in Vβ4+CD8+ T Cell Activation Associated with Latent Murine Gammaherpesvirus Infection. J Immunol 163: 3403–3408.

72. FlañoE, WoodlandDL, BlackmanMA, DohertyPC (2001) Analysis of Virus-Specific CD4+ T Cells during Long-Term Gammaherpesvirus Infection. J Virol 75: 7744–7748 doi:10.1128/JVI.75.16.7744-7748.2001

73. FreemanML, BurkumCE, LanzerKG, JensenMK, AhmedM, et al. (2011) Cutting Edge: Activation of Virus-Specific CD4 T Cells throughout γ-Herpesvirus Latency. J Immunol 187: 6180–6184 doi:10.4049/jimmunol.1102745

74. ChenT, HudnallSD (2006) Anatomical mapping of human herpesvirus reservoirs of infection. Mod Pathol 19: 726–737.

75. CorbellinoM, PoirelL, BestettiG, PizzutoM, AubinJT, et al. (1996) Restricted Tissue Distribution of Extralesional Kaposi's Sarcoma-Associated Herpesvirus-Like DNA Sequences in AIDS Patients with Kaposi's Sarcoma. Aids Res Hum Retroviruses 12: 651–657 doi:10.1089/aid.1996.12.651

76. LuppiM, BarozziP, SchulzTF, SettiG, StaskusK, et al. (2000) Bone Marrow Failure Associated with Human Herpesvirus 8 Infection after Transplantation. N Engl J Med 343: 1378–1385 doi:10.1056/NEJM200011093431905

77. KikutaH, SakiyamaY, MatsumotoS, Oh-IshiT, NakanoT, et al. (1993) Fatal Epstein-Barr virus-associated hemophagocytic syndrome. Blood 82: 3259–3264.

78. HoangMP, DawsonDB, RogersZR, ScheuermannRH, RogersBB (1998) Polymerase chain reaction amplification of archival material for epstein-barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19 in children with bone marrow hemophagocytosis. Hum Pathol 29: 1074–1077 doi:10.1016/S0046-8177(98)90416-6

79. FrizzeraG, HantoDW, Gajl-PeczalskaKJ, RosaiJ, McKennaRW, et al. (1981) Polymorphic diffuse B-cell hyperplasias and lymphomas in renal transplant recipients. Cancer Res 41: 4262–4279.

80. HantoDW, FrizzeraG, Gajl-PeczalskaKJ, SimmonsRL (1985) Epstein-Barr virus, immunodeficiency, and B cell lymphoproliferation. Transplantation 39: 461–472.

81. Purtilo D (1984) Immune Deficiency and Cancer: Epstein-Barr Virus and Lymphoproliferative Malignancies. Springer

82. ShapiroRS, McClainK, FrizzeraG, Gajl-PeczalskaKJ, KerseyJH, et al. (1988) Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation. Blood 71: 1234–1243.

83. WatanabeH, KoideM, FukuchiK, TakagiY, TomoyasuS, et al. (1997) Presence of Epstein-Barr virus genome in the bone marrow of patients with hematopoietic malignancies. Acta Haematol 98: 32–36.

84. ZutterMM, MartinPJ, SaleGE, ShulmanHM, FisherL, et al. (1988) Epstein-Barr virus lymphoproliferation after bone marrow transplantation. Blood 72: 520–529.

85. GrillotDA, MerinoR, PenaJC, FanslowWC, FinkelmanFD, et al. (1996) Bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice. J Exp Med 183: 381–391 doi:10.1084/jem.183.2.381

86. FlanoE, HusainSM, SampleJT, WoodlandDL, BlackmanMA (2000) Latent Murine {gamma}-Herpesvirus Infection Is Established in Activated B Cells, Dendritic Cells, and Macrophages. J Immunol 165: 1074–1081.

87. FlanoE, KimI-J, MooreJ, WoodlandDL, BlackmanMA (2003) Differential {gamma}-Herpesvirus Distribution in Distinct Anatomical Locations and Cell Subsets During Persistent Infection in Mice. J Immunol 170: 3828–3834.

88. WeckKE, KimSS, VirginHW, SpeckSH (1999) Macrophages Are the Major Reservoir of Latent Murine Gammaherpesvirus 68 in Peritoneal Cells. J Virol 73: 3273–3283.

89. WatanabeK, IchinoseS, HayashizakiK, TsubataT (2008) Induction of autophagy by B cell antigen receptor stimulation and its inhibition by costimulation. Biochem Biophys Res Commun 374: 274–281 doi:10.1016/j.bbrc.2008.07.013

90. McLeodIX, HeY (2010) Roles of autophagy in lymphocytes: reflections and directions. Cell Mol Immunol 7: 104–107 doi:10.1038/cmi.2009.115

91. TangyeSG, TarlintonDM (2009) Memory B cells: Effectors of long-lived immune responses. Eur J Immunol 39: 2065–2075 doi:10.1002/eji.200939531

92. MaruyamaM, LamKP, RajewskyK (2000) Memory B-cell persistence is independent of persisting immunizing antigen. Nature 407: 636–642 doi:10.1038/35036600

93. CrottyS, FelgnerP, DaviesH, GlidewellJ, VillarrealL, et al. (2003) Cutting edge: long-term B cell memory in humans after smallpox vaccination. J Immunol Baltim Md 1950 171: 4969–4973.

94. GrayD, SkarvallH (1988) B–cell memory is short-lived in the absence of antigen. Nature 336: 70–73 doi:10.1038/336070a0

95. DohertyPC, ChristensenJP, BelzGT, StevensonPG, SangsterMY (2001) Dissecting the host response to a gamma-herpesvirus. Philos Trans R Soc Lond B Biol Sci 356: 581–593 doi:10.1098/rstb.2000.0786

96. StevensonPG, MayJS, SmithXG, MarquesS, AdlerH, et al. (2002) K3-mediated evasion of CD8(+) T cells aids amplification of a latent gamma-herpesvirus. Nat Immunol 3: 733–740 doi:10.1038/ni818

97. Ragona G, Tabilio A, Fruscalzo A, Annino L, Angeloni A, et al.. (1988) Presence of EBV infected cells in the bone marrow from transplant donors. In: Ablashi DV, Ariad A, Krueger GRF, Pagano JS, Pearson GR, editors. Epstein-Barr Virus and Human Disease. Clifton, NJ: Humana Press. pp. 231–235.

98. DeegHJ, SocieG (1998) Malignancies After Hematopoietic Stem Cell Transplantation: Many Questions, Some Answers. Blood 91: 1833–1844.

99. HenryM, UthmanA, GeusauA, RiegerA, FurciL, et al. (1999) Infection of Circulating CD34+ Cells by HHV-8 in Patients with Kaposi/'s Sarcoma. 113: 613–616.

100. Bertolini L, Falzetti F, Lanzilli G, Moscone O, Longo M, et al.. (1991) Lymphocyte receptors as differentiation markers in a cell line autonomously arisen “in vitro” from a human normal bone marrow. In: Wegmann RJ, Wegmann MA, editors. Recent Advances in Cellular and Molecular Biology. Leuven, Belgium: Peeter Press, Vol. 1. pp. 77–89.

101. BertoliniL, AebischerML, AmeglioF, AngeloniA, DelarocheI, et al. (2005) Phenotypic and genotypic characteristics of new euploid-diploid lymphoblastoid B cell lines EBV+, normal human bone marrow derived, spontaneously overgrown in vitro. J Virol Methods 126: 91–100 doi:10.1016/j.jviromet.2005.01.029

102. PavlovaBG, MühlbergerHH, StroblH, GrillR, HaslbergerA, et al. (1995) B lymphocytes with latent EBV infection appearing in long-term bone marrow cultures (HLTBMCs) from haematological patients induce lysis of stromal microenvironment. Br J Haematol 89: 704–711.

103. FacerCA, PlayfairJH (1989) Malaria, Epstein-Barr virus, and the genesis of lymphomas. Adv Cancer Res 53: 33–72.

104. MorrowRHJr (1985) Epidemiological evidence for the role of falciparum malaria in the pathogenesis of Burkitt's lymphoma. Iarc Sci Publ 177–186.

105. AsitoAS, PiriouE, JuraWG, OumaC, OdadaPS, et al. (2011) Suppression of circulating IgD+CD27+ memory B cells in infants living in a malaria-endemic region of Kenya. Malar J 10: 362 doi:10.1186/1475-2875-10-362

106. PiriouE, AsitoAS, SumbaPO, FioreN, MiddeldorpJM, et al. (2012) Early Age at Time of Primary Epstein–Barr Virus Infection Results in Poorly Controlled Viral Infection in Infants From Western Kenya: Clues to the Etiology of Endemic Burkitt Lymphoma. J Infect Dis 205: 906–913 doi:10.1093/infdis/jir872

107. DeheeA, AsselotC, PiolotT, JacometC, RozenbaumW, et al. (2001) Quantification of Epstein-Barr virus load in peripheral blood of human immunodeficiency virus-infected patients using real-time PCR. J Med Virol 65: 543–552 doi:10.1002/jmv.2071

108. RichardY, AmielC, JeantilsV, MestivierD, PortierA, et al. (2010) Changes in Blood B Cell Phenotypes and Epstein-Barr Virus Load in Chronically Human Immunodeficiency Virus—Infected Patients before and after Antiretroviral Therapy. J Infect Dis 202: 1424–1434 doi:10.1086/656479

109. ToussirotÉ, RoudierJ (2008) Epstein–Barr virus in autoimmune diseases. Best Pract Res Clin Rheumatol 22: 883–896 doi:10.1016/j.berh.2008.09.007

110. PosnettDN (2008) Herpesviruses and autoimmunity. Curr Opin Investig Drugs Lond Engl 2000 9: 505–514.

111. GetahunA, SmithMJ, KogutI, DykLFvan, CambierJC (2012) Retention of Anergy and Inhibition of Antibody Responses during Acute Gammaherpesvirus 68 Infection. J Immunol 189: 2965–2974 doi:10.4049/jimmunol.1201407

112. SmithKA, EfstathiouS, CookeA (2007) Murine gammaherpesvirus-68 infection alters self-antigen presentation and type 1 diabetes onset in NOD mice. J Immunol Baltim Md 1950 179: 7325–7333.

113. YarilinDA, ValiandoJ, PosnettDN (2004) A Mouse Herpesvirus Induces Relapse of Experimental Autoimmune Arthritis by Infection of the Inflammatory Target Tissue. J Immunol 173: 5238–5246.

114. PeacockJW, ElsawaSF, PettyCC, HickeyWF, BostKL (2003) Exacerbation of experimental autoimmune encephalomyelitis in rodents infected with murine gammaherpesvirus-68. Eur J Immunol 33: 1849–1858 doi:10.1002/eji.200323148

115. LiH, IkutaK, SixbeyJW, TibbettsSA (2008) A Replication-Defective Gammaherpesvirus Efficiently Establishes Long-Term Latency in Macrophages but Not in B Cells In Vivo. J Virol 82: 8500–8508 doi:10.1128/JVI.00186-08

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 2
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