Biology Bulletin Reviews

, Volume 8, Issue 2, pp 114–123 | Cite as

Specific Features of Apoptotic Signaling Regulation in Cells Infected with Cytomegalovirus and Epstein–Barr Virus

  • N. A. Sakharnov
  • O. V. Utkin
  • D. I. Knyazev
  • E. N. Filatova
  • V. D. Tsvetkova


A large proportion of global population is infected with lymphotropic herpesviruses—cytomegalovirus (CMV) and Epstein–Barr virus (EBV). The products of CMV and EBV gene expression influence various elements of the apoptosis signaling pathways in infected cells and result in successful virus persistence. Some specific features in the interaction of CMV and EBV proteins and RNA transcripts with cellular proteins of apoptosis signaling pathways are considered. The review focuses on the structural and functional elements of the apoptosis-associated signaling pathways that are affected by these viruses.


cytomegalovirus Epstein–Barr virus apoptosis signaling pathways programmed cell death 


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  1. Adler, B. and Sinzger, C., Endothelial cells in human cytomegalovirus infection: one host cell out of many or a crucial target for virus spread? Thromb. Haemostasis, 2009, vol. 102, no. 6, pp. 1057–1063.Google Scholar
  2. Amundson, S.A., Myers, T.G., and Fornace, A.J., Jr., Roles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress, Oncogene, 1998, vol. 17, pp. 3287–3299.PubMedCrossRefGoogle Scholar
  3. Anderton, E., Yee, J., Smith, P., et al., Two Epstein–Barr virus (EBV) oncoproteins cooperate to repress expression of the proapoptotic tumor-suppressor Bim: clues to the pathogenesis of Burkitt’s lymphoma, Oncogene, 2008, vol. 27, no. 4, pp. 421–433.PubMedCrossRefGoogle Scholar
  4. Bellows, D.S., Howell, M., Pearson, C., et al., Epstein–Barr virus BALF1 is a BCL-2-like antagonist of the herpesvirus antiapoptotic BCL-2 proteins, J. Virol., 2002, vol. 76, no. 5, pp. 2469–2479.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Blokhin, D.Yu., Sokolovskaya, A.A., Mikhailov, A.D., et al., CD95-induced apoptosis and multiresistant phenotype of human lymphoblastoid T-cells, Ross. Bioter. Zh., 2003, vol. 2, no. 3, pp. 37–46.Google Scholar
  6. Bonin, L.R. and McDougall, J.K., Human cytomegalovirus IE2 86-kilodalton protein binds p53 but does not abrogate G1 checkpoint function, J. Virol., 1997, vol. 71, pp. 5861–5870.PubMedPubMedCentralGoogle Scholar
  7. Brune, W., Inhibition of programmed cell death by cytomegaloviruses, Virus Res., 2011, vol. 157, pp. 144–150.PubMedCrossRefGoogle Scholar
  8. Cai, X., Schafer, A., Lu, S., et al., Epstein–Barr virus microRNAs are evolutionarily conserved and differen tially expressed, PLoS Pathog., 2006, vol. 2, no. 3, p. e23.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Carmilleri-Broet, B.S., Davi, F., Feuillard, J., et al., High expression of latent membrane protein 1 of Epstein–Barr virus and Bcl-2 oncoprotein in acquired immunodeficiency syndrome-related primary brain lymphomas, Blood, 1995, vol. 86, no. 2, pp. 432–435.Google Scholar
  10. Chakrabarti, A., Chen, A.W., and Varner, J.D., A review of the mammalian unfolded protein response, Biotechnol. Bioeng., 2011, vol. 108, pp. 2777–2793.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Chen, C., Li, D., and Guo, N., Regulation of cellular and viral protein expression by the Epstein–Barr virus transcriptional regulator Zta: implications for therapy of EBV associated tumors, Cancer Biol. Ther., 2009, vol. 8, no. 11, pp. 987–995.PubMedCrossRefGoogle Scholar
  12. Chiou, S.H., Yang, Y.P., Lin, J.C., et al., The immediate early 2 protein of human cytomegalovirus (HCMV) mediates the apoptotic control in HCMV retinitis through up-regulation of the cellular FLICE-inhibitory protein expression, J. Immunol., 2006, vol. 177, pp. 6199–6206.PubMedCrossRefGoogle Scholar
  13. Choy, E.Y., Siu, K.L., Kok, K.H., et al., An Epstein–Barr virusencoded microRNA targets Puma to promote host cell survival, J. Exp. Med., 2008, vol. 205, no. 11, pp. 2551–2560.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Cohen, J.I. and Lekstrom, K., Epstein–Barr virus BARF1 protein is dispensable for B-cell transformation and inhibits alpha interferon secretion from mononuclear cells, J. Virol., 1999, vol. 73, no. 9, pp. 7627–7632.PubMedPubMedCentralGoogle Scholar
  15. Cross, J.R., Postigo, A., Blight, K., and Downward, J., Viral pro-survival proteins block separate stages in Bax activation but changes in mitochondrial ultrastructure still occur, Cell Death Diff., 2008, vol. 15, no. 6, pp. 997–1008.CrossRefGoogle Scholar
  16. Dempsey, P.W., Doyle, S.E., He, J.Q., et al., The signaling adaptors and pathways activated by TNF superfamily, Cytokine Growth Factor Rev., 2003, vol. 14, pp. 193–209.PubMedCrossRefGoogle Scholar
  17. Desbien, A.L., Kappler, J.W., and Marrack, P., The Epstein–Barr virus Bcl-2 homolog, BHRF1, blocks apoptosis by binding to a limited amount of Bim, Proc. Natl. Acad. Sci. U.S.A., 2009, vol. 106, no. 14, pp. 5663–5668.PubMedGoogle Scholar
  18. Dewson, G., Kratina, T., Sim, H.W., et al., To trigger apoptosis, Bak exposes its BH3 domain and homodimerizes via BH3: groove interactions, Mol. Cell, 2008, vol. 30, pp. 369–380.PubMedGoogle Scholar
  19. Dreyfus, D.H., Nagasawa, M., Pratt, J.C., et al., Inactivation of NF-kB by EBV BZLF-1-encoded ZEBRA protein in human T cells, J. Immunol., 1999, vol. 163, no. 11, pp. 6261–6268.PubMedGoogle Scholar
  20. Electronic epidemiological atlas of the Volga Federal District. Accessed January 20, 2017.Google Scholar
  21. Filatova, E.N. and Utkin, O.V., Modern approaches to the modeling of herpesvirus infection, Medial’, 2014, vol. 2, no. 12, pp. 172–197.Google Scholar
  22. Finke, J., Fritzen, R., Ternes, P., et al., Expression of bcl-2 in Burkitt’s lymphoma cell lines: induction by latent Epstein–Barr virus genes, Blood, 1992, vol. 80, no. 2, pp. 459–469.PubMedGoogle Scholar
  23. Fliss, P.M. and Brune, W., Prevention of cellular suicide by cytomegaloviruses, Viruses, 2012, vol. 4, pp. 1928–1949.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Floettmann, J.E. and Rowe, M., Epstein–Barr virus latent membrane protein-1 (LMP1) C-terminus activation region 2 (CTAR2) maps to the far C-terminus and requires oligomerisation for NF-?B activation, Oncogene, 1997, vol. 15, pp. 1851–1858.PubMedCrossRefGoogle Scholar
  25. Fu, Q., He, C., and Mao, Z.R., Epstein–Barr virus interactions with the Bcl-2 protein family and apoptosis in human tumor cells, J. Zhejiang Univ. Sci. Biomed. Biotech., 2013, vol. 14, no. 1, pp. 8–24.CrossRefGoogle Scholar
  26. Gerna, G., Zipeto, D., Percivalle, E., et al., Human cytomegalovirus infection of the major leukocyte subpopulations and evidence for initial viral replication in polymorphonuclear leukocytes from viremic patients, J. Infect. Dis., 1992, vol. 166, no. 6, pp. 1236–1244.PubMedCrossRefGoogle Scholar
  27. Gires, O., Zimber-Strobl, U., Gonnella, R., et al., Latent membrane protein 1 of Epstein–Barr virus mimics a constitutively active receptor molecule, EMBO J., 1997, vol. 16, pp. 6131–6140.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Goldmacher, V.S., Bartle, L.M., Skaletskaya, A., et al., A cytomegalovirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2, Proc. Natl. Acad. Sci. U.S.A., 1999, vol. 96, pp. 12536–12541.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Golks, A., Brenner, D., Fritsch, C., et al., c-FLIPR, a new regulator of death receptor-induced apoptosis, J. Biol. Chem., 2005, vol. 280, no. 15, pp. 14507–14513.Google Scholar
  30. Green, D.R. and Reed, J.C., Mitochondria and apoptosis, Science, 1998, vol. 281, pp. 1309–1312.PubMedCrossRefGoogle Scholar
  31. Grefte, A., Blom, N., van der Giessen, M., et al., Ultrastructural analysis of circulating cytomegalic cells in patients with active cytomegalovirus infection: evidence for virus production and endothelial origin, J. Infect. Dis., 1993, vol. 168, no. 5, pp. 1110–1118.PubMedCrossRefGoogle Scholar
  32. Hayward, S.D., Viral interactions with the Notch pathway, Semin. Cancer Biol., 2004, vol. 14, no. 5, pp. 387–396.PubMedCrossRefGoogle Scholar
  33. Hehlgans, T. and Pfeffer, K., The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games, J. Immunol., 2005, vol. 115, pp. 1–20.Google Scholar
  34. Hickish, T., Robertson, D., Clarke, P., et al., Ultrastructural localization of BHRF1: an Epstein–Barr virus gene product which has homology with bcl-2, Cancer Res., 1994, vol. 54, pp. 2808–2811.PubMedGoogle Scholar
  35. Howe, J.G. and Steitz, J.A., Localization of Epstein–Barr virus-encoded small RNAs by in situ hybridization, Proc. Natl. Acad. Sci. U.S.A., 1986, vol. 83, pp. 9006–9010.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Isler, J.A., Skalet, A.H., and Alwine, J.C., Human cytomegalovirus infection activates and regulates the unfolded protein response, J. Virol., 2005, vol. 79, pp. 6890–6899.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Kalla, M., Schmeinck, A., Bergbauer, M., et al., AP-1 homolog BZLF1 of Epstein–Barr virus has two essential functions dependent on the epigenetic state of the viral genome, Proc. Natl. Acad. Sci. U.S.A., 2010, vol. 107, no. 2, pp. 850–855.PubMedCrossRefGoogle Scholar
  38. Keating, S., Prince, S., Jones, M., and Rowe, M., The lytic cycle of Epstein–Barr virus is associated with decreased expression of cell surface major histocompatibility complex class I and class II molecules, J. Virol., 2002, vol. 76, no. 16, pp. 8179–8188.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Kelly, G.L., Long, H.M., and Stylianou, J., An Epstein–Barr virus anti-apoptotic protein constitutively expressed in transformed cells and implicated in Burkitt’s lymphomagenesis: the WP/BHRF1 link, PLoS Pathog., 2009, vol. 5, no. 3, p. e1000341.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Kenney, J.L., Guinness, M.E., Curiel, T., and Lacy, J., Antisense to the Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1) suppresses LMP-1 and bcl-2 expression and promotes apoptosis in EBVimmortalized B cells, Blood, 1998, vol. 92, no. 5, pp. 1721–1727.PubMedGoogle Scholar
  41. Kieff, E. and Rickinson, A.B., Epstein–Barr virus and its replication, in Fields Virology, Knipe, D.M. and Howley, P.M., Eds., Philadelphia: Lippincott Williams and Wilkins, 2007, pp. 2603–2654.Google Scholar
  42. Kiener, P.A., Davis, P.M., Staring, G.C., et al., Differential induction of apoptosis by Fas–Fas-ligand interactions in human monocytes and macrophages, J. Exp. Med., 1997, vol. 185, pp. 1511–1516.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Kim, S., Yu, S.S., and Kim, V.N., Essential role of NF-kB in transactivation of the human immunodeficiency virus long terminal repeat by the human cytomegalovirus 1E1 protein, J. Gen. Virol., 1996, vol. 77, pp. 83–91.PubMedCrossRefGoogle Scholar
  44. Ko, L.J. and Prives, C., p53: puzzle and paradigm, Genes Dev., 1996, vol. 10, pp. 1054–1072.PubMedCrossRefGoogle Scholar
  45. Kohlhof, H., Hampel, F., Hoffmann, R., et al., Notch1, Notch2, and Epstein–Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein–Barr virus-infected B cells, Blood, 2009, vol. 113, no. 22, pp. 5506–5515.PubMedGoogle Scholar
  46. Komano, J., Maruo, S., Kurozumi, K., et al., Oncogenic role of Epstein–Barr virus-encoded RNAs in Burkitt’s lymphoma cell line akata, J. Virol., 1999, vol. 73, no. 12, pp. 9827–9831.PubMedPubMedCentralGoogle Scholar
  47. Kuskova, T.K. and Belova, E.G., Modern herpesvirus family, Lech. Vrach, 2004, no. 5, pp. 64–69.Google Scholar
  48. Kuwana, T., Bouchier-Hayes, L., Chipuk, J.E., et al., BH3 domains of BH3-only proteins differentially regulate Baxmediated mitochondrial membrane permeabilization both directly and indirectly, Mol. Cell, 2005, vol. 17, pp. 525–535.PubMedCrossRefGoogle Scholar
  49. Kvansakul, M., Wei, A.H., Fletcher, J.I., et al., Structural basis for apoptosis inhibition by Epstein–Barr virus BHRF1, PLoS Pathog., 2010, vol. 6, no. 12, pp. 1–10.CrossRefGoogle Scholar
  50. Le Clorennec, C., Youlyouz-Marfak, I., Adriaenssens, E., et al., EBV latency III immortalization program sensitizes B cells to induction of CD95-mediated apoptosis via LMP1: role of NF-?B, STAT1, and p53, Blood, 2006, vol. 107, pp. 2070–2078.PubMedCrossRefGoogle Scholar
  51. Le Clorennec, C., Ouk, T.S., Youlyouz-Marfak, I., et al., Molecular basis of cytotoxicity of Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) in EBV latency III b cells: LMP1 induces type II ligand-independent autoactivation of CD95/Fas with caspase 8- mediated apoptosis, J. Virol., 2008, vol. 82, no. 13, pp. 6721–6733.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Le, V.T., Trilling, M., and Hengel, H., The cytomegaloviral protein pUL138 acts as potentiator of tumor necrosis factor (TNF) receptor 1 surface density to enhance ULb-encoded modulation of TNF-signaling, J. Virol., 2011, vol. 85, no. 24, pp. 13260–13270.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Lei, K. and Davis, R.J., JNK phosphorylation of Bimrelated members of the Bcl2 family induces Bax-dependent apoptosis, Proc. Natl. Acad. Sci. U.S.A., 2003, vol. 100, pp. 2432–2437.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Li, X. and Bhaduri-McIntosh, S., A central role for STAT3 in gammaherpesvirus-life cycle and -diseases, Front. Microbiol., 2016, vol. 7, art. 1052.Google Scholar
  55. Marshall, W.L., Yim, C., Gustafson, E., et al., Epstein–Barr virus encodes a novel homolog of the bcl-2 oncogene that inhibits apoptosis and associates with Bax and Bak, J. Virol., 1999, vol. 73, no. 6, pp. 5181–5185.PubMedPubMedCentralGoogle Scholar
  56. McCormick, A.L., Skaletskaya, A., Barry, P.A., et al., Differential function and expression of the viral inhibitor of caspase 8-induced apoptosis (vICA) and the viral mitochondria- localized inhibitor of apoptosis (vMIA) cell death suppressors conserved in primate and rodent cytomegaloviruses, Virology, 2003, vol. 316, pp. 221–233.PubMedCrossRefGoogle Scholar
  57. McCormick, A.L., Roback, L., Livingston-Rosanoff, D., and St. Clair, C., The human cytomegalovirus UL36 gene controls caspase-dependent and -independent cell death programs activated by infection of monocytes differentiating to macrophages, J. Virol., 2010, vol. 84, pp. 5108–5123.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Morrison, T.E. and Kenney, S.C., BZLF1, an Epstein–Barr virus immediate-early protein, induces p65 nuclear translocation while inhibiting p65 transcriptional function, Virology, 2004, vol. 328, no. 2, pp. 219–232.Google Scholar
  59. Niedobitek, G., Young, L.S., and Herbst, H., Epstein–Barr virus infection and the pathogenesis of malignant lymphomas, Cancer Surv., 1997, vol. 30, pp. 143–162.PubMedGoogle Scholar
  60. O’Brien, V. Viruses and apoptosis, J. Gen. Virol., 1998, vol. 79, pp. 1833–1845.PubMedCrossRefGoogle Scholar
  61. Oldstone, M.B., How viruses escape from cytotoxic T lymphocytes: molecular parameters and players, Virology, 1997, vol. 234, no. 2, pp. 179–185.PubMedCrossRefGoogle Scholar
  62. Paschos, K., Smith, P., Anderton, E., et al., Epstein–Barr virus latency in B cells leads to epigenetic repression and CpG methylation of the tumor suppressor gene bim, PLoS Pathog., 2009, vol. 5, no. 6, p. e1000492.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Paschos, K., Parker, G.A., Watanatanasup, E., et al., BIM promoter directly targeted by EBNA3C in polycombmediated repression by EBV, Nucleic Acids Res., 2012, vol. 40, no. 15, pp. 7233–7246.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Pauleau, A.L., Larochette, N., Giordanetto, F., et al., Structurefunction analysis of the interaction between Bax and the cytomegalovirus-encoded protein vMIA, Oncogene, 2007, vol. 26, pp. 7067–7080.PubMedCrossRefGoogle Scholar
  65. Paulus, C. and Nevels, M., The human cytomegalovirus major immediate-early proteins as antagonists of intrinsic and innate antiviral host responses, Viruses, 2009, vol. 1, pp. 760–779.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Plachter, B., Sinzger, C., and Jahn, G., Cell types involved in replication and distribution of human cytomegalovirus, Adv. Virus Res., 1996, vol. 46, pp. 195–261.PubMedCrossRefGoogle Scholar
  67. Portis, T. and Longnecker, R., Epstein–Barr virus (EBV) LMP2A mediates B-lymphocyte survival through constitutive activation of the Ras/PI3K/AKT pathway, Oncogene, 2004, vol. 23, no. 53, pp. 8619–8628.PubMedCrossRefGoogle Scholar
  68. Powers, C., De Filippis, V., Malouli, D., and Fruh, K., Cytomegalovirus immune evasion, Curr. Topics Microbiol. Immunol., 2008, vol. 325, pp. 333–359.Google Scholar
  69. Pratt, Z.L., Zhang, J., and Sugden, B., Simultaneously induce and inhibit oncogene of Epstein–Barr virus can the latent membrane protein 1 (LMP1) apoptosis in B cells, J. Virol., 2012, vol. 86, no. 8, pp. 4380–4393.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Putcha, G.V., Le, S., Frank, S., et al., JNK-mediated BIM phosphorylation potentiates BAX-dependent apoptosis, Neuron, 2003, vol. 38, pp. 899–914.PubMedCrossRefGoogle Scholar
  71. Reed, J.C., Doctor, K.S., and Goldzik, A., The domain of apoptosis: a genomic perspective, Sci. Signaling, 2004, vol. 239, pp. 1–29.Google Scholar
  72. Reeves, M.B., Davies, A.A., McSharry, B.P., et al., Complex I binding by a virally encoded RNA regulates mitochondria- induced cell death, Science, 2007, vol. 316, no. 5829, pp. 1345–1348.PubMedCrossRefGoogle Scholar
  73. Reinke, P., Fietze, E., Ode-Hakim, S., et al., Late-acute renal allograft rejection and symptomless cytomegalovirus infection, Lancet, 1994, vol. 344, nos. 8939–8940, pp. 1737–1738.PubMedCrossRefGoogle Scholar
  74. Schneider, F., Neugebauer, J., Griese, J., et al., The viral oncoprotein LMP1 exploits TRADD for signaling by masking its apoptotic activity, PLoS Biol., 2008, vol. 6, no. 1, p. e8.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Schulze-Osthoff, K., Ferrari, D., Los, M., et al., Apoptosis signaling by death receptors, Eur. J. Biochem., 1998, vol. 254, pp. 439–459.PubMedCrossRefGoogle Scholar
  76. Schütze, S., Tchikov, V., and Schneider-Brachert, W., Regulation of TNFR1 and CD95 signalling by receptor compartmentalization, Nat. Rev. Mol. Cell Biol., 2008, vol. 9, no. 8, pp. 655–662.PubMedCrossRefGoogle Scholar
  77. Seto, E., Moosmann, A., Gromminger, S., et al., Micro RNAs of Epstein–Barr virus promote cell cycle progression and prevent apoptosis of primary human B cells, PLoS Pathog., 2010, vol. 6, p. e1001063.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Sheng, W., Decaussin, G., Sumner, S., and Ooka, T., N-terminal domain of BARF1 gene encoded by Epstein–Barr virus is essential for malignant transformation of rodent fibroblasts and activation of BCL-2, Oncogene, 2001, vol. 20, no. 10, pp. 1176–1185.PubMedCrossRefGoogle Scholar
  79. Sinzger, C., Plachter, B., Grefte, A., et al., Tissue macrophages are infected by human cytomegalovirus in vivo, J. Infect. Dis., 1996, vol. 173, no. 1, pp. 240–245.PubMedCrossRefGoogle Scholar
  80. Sinzger, C., Digel, M., and Jahn, G., Cytomegalovirus cell tropism, Curr. Topics Microbiol. Immunol., 2008, vol. 325, pp. 63–83.Google Scholar
  81. Skaletskaya, A., Bartle, L.M., Chittenden, T., et al., A cytomegalovirus- encoded inhibitor of apoptosis that suppresses caspase-8 activation, Proc. Natl. Acad. Sci. U.S.A., 2001, vol. 98, pp. 7829–7834.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Somova, L.M., Besednova, N.N., and Plekhova, N.G., Apoptosis and infectious diseases, Infekts. Immun., 2014, vol. 4, no. 4, pp. 303–318.Google Scholar
  83. Speir, E., Modali, R., Huang, E.S., et al., Potential role of human cytomegalovirus and p53 interaction in coronary restenosis, Science, 1994, vol. 265, pp. 391–394.PubMedCrossRefGoogle Scholar
  84. Steelman, L.S., Pohnert, S.C., Shelton, J.G., et al., JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCRABL in cell cycle progression and leukemogenesis, Leukemia, 2004, vol. 18, no. 2, pp. 189–218.PubMedCrossRefGoogle Scholar
  85. Strockbine, L.D., Cohen, J.I., Farrah, T., et al., The Epstein–Barr virus BARF1 gene encodes a novel, soluble colonystimulating factor-1 receptor, J. Virol., 1998, vol. 72, no. 5, pp. 4015–4021.Google Scholar
  86. Szegezdi, E., Logue, S.E., Gorman, A.M., and Samali, A., Mediators of endoplasmic reticulum stress-induced apoptosis, EMBO Rep., 2006, vol. 7, pp. 880–885.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Terhune, S., Torigoi, E., Moorman, N., et al., Human cytomegalovirus UL38 protein blocks apoptosis, J. Virol., 2007, vol. 81, pp. 3109–3123.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Thome, M., Schneider, P., Hofmann, K., et al., Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors, Nature, 1997, vol. 386, no. 6624, pp. 517–521.PubMedCrossRefGoogle Scholar
  89. Thorley-Lawson, D.A. and Babcock, J.G., A model for persistent infection with Epstein–Barr virus: the stealth virus of human B cells, Life Sci., 1999, vol. 65, no. 14, pp. 1433–1453.PubMedCrossRefGoogle Scholar
  90. Tomkinson, B., Robertson, E., and Kieff, E., Epstein–Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation, J. Virol., 1993, vol. 67, no. 4, pp. 2014–2025.PubMedPubMedCentralGoogle Scholar
  91. Urano, F., Wang, X., Bertolotti, A., et al., Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1, Science, 2000, vol. 287, pp. 664–666.PubMedCrossRefGoogle Scholar
  92. Uren, R.T., Dewson, G., Chen, L., et al., Mitochondrial permeabilization relies on BH3 ligands engaging multiple prosurvival Bcl-2 relatives, not Bak, J. Cell Biol., 2007, vol. 177, pp. 277–287.PubMedCrossRefGoogle Scholar
  93. Utkin, O.V. and Novikov, V.V., Regulation of apoptosis by alternative splicing of matrix RNA, Ross. Bioter. Zh., 2007, vol. 6, no. 2, pp. 13–20.Google Scholar
  94. Utkin, O.V. and Novikov, V.V., Role of receptors of death in apoptosis modulation, Usp. Sovrem. Biol., 2012, vol. 132, no. 4, pp. 381–390.Google Scholar
  95. Wang, S., Rowe, M., and Lundgren, E., Expression of the Epstein–Barr virus transforming protein LMP1 causes a rapid and transient stimulation of the Bcl-2 homologue Mcl-1 levels in B-cell lines, Cancer Res., 1996, vol. 56, pp. 4610–4613.PubMedGoogle Scholar
  96. Westphal, D., Dewson, G., Czabotar, P.E., and Kluck, R.M., Molecular biology of Bax and Bak activation and action, Biochim. Biophys. Acta, 2011, vol. 1813, pp. 521–531.PubMedCrossRefGoogle Scholar
  97. Williams, E.J., Embleton, N.D., Clark, J.E., et al., Viral infections: contributions to late fetal death, stillbirth, and infant death, J. Pediatr., 2013, vol. 163, no. 2, pp. 424–428.PubMedGoogle Scholar
  98. Womack, J. and Jimenez, M., Common questions about infectious mononucleosis, Am. Fam. Physician, 2015, vol. 91, no. 6, pp. 372–376.PubMedGoogle Scholar
  99. Wong, H.L., Wang, X., Chang, R.C., et al., Stable expression of EBERs in immortalized nasopharyngeal epithelial cells confers resistance to apoptotic stress, Mol. Carcinog., 2005, vol. 44, no. 2, pp. 92–101.PubMedCrossRefGoogle Scholar
  100. Xuan, B., Qian, Z., Torigoi, E., and Yu, D., Human cytomegalovirus protein pUL38 induces ATF4 expression, inhibits persistent JNK phosphorylation, and suppresses endoplasmic reticulum stress-induced cell death, J. Virol., 2009, vol. 83, pp. 3463–3474.PubMedGoogle Scholar
  101. Zhao, J., Sinclair, J., Houghton, J., et al., Cytomegalovirus 2.7 RNA transcript protects endothelial cells against apoptosis during ischemia/reperfusion injury, J. Heart Lung Transplant., 2010, vol. 29, no. 3, pp. 342–345.PubMedCrossRefGoogle Scholar
  102. Zhu, H., Shen, Y., and Shenk, T., Human cytomegalovirus IE1 and IE2 proteins block apoptosis, J. Virol., 1995, vol. 69, pp. 7960–7970.PubMedPubMedCentralGoogle Scholar
  103. Zimber-Strobl, U. and Strobl, L.J., EBNA2 and Notch signaling in Epstein–Barr virus mediated immortalization of B lymphocytes, Semin. Cancer Biol., 2001, vol. 11, no. 6, pp. 423–434.PubMedCrossRefGoogle Scholar
  104. Zuo, J., Thomas, W.A., Haigh, T.A., et al., Epstein–Barr virus evades CD4+ T cell responses in lytic cycle through BZLF1-mediated down-regulation of CD74 and the cooperation of vBcl-2, PLoS Pathog., 2011, vol. 7, no. 12, p. e1002455.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • N. A. Sakharnov
    • 1
  • O. V. Utkin
    • 1
    • 2
  • D. I. Knyazev
    • 1
  • E. N. Filatova
    • 1
  • V. D. Tsvetkova
    • 1
  1. 1.Blokhina Institute of Epidemiology and MicrobiologyFederal Service on Surveillance for Consumer Rights Protection and Human WelfareNizhny NovgorodRussia
  2. 2.Nizhny Novgorod State Medical AcademyMinistry of Public Health of the Russian FederationNizhny NovgorodRussia

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