Tumor Microenvironment Conditioning by Abortive Lytic Replication of Oncogenic γ-Herpesviruses

  • Christian MünzEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1225)


Epstein Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) constitute the human γ-herpesviruses and two of the seven human tumor viruses. In addition to their viral oncogenes that primarily belong to the latent infection programs of these viruses, they encode proteins that condition the microenvironment. Many of these are early lytic gene products and are only expressed in a subset of infected cells of the tumor mass. In this chapter I will describe their function and the evidence that targeting them in addition to the latent oncogenes could be beneficial for the treatment of EBV- and KSHV-associated malignancies.


Kaposi sarcoma-associated herpesvirus Epstein Barr virus Viral IL-6 Viral IL-10 Viral MIP Viral miRNA CCL5 Lytic replication Angiogenesis Kaposi sarcoma Primary effusion lymphoma Multicentric Castleman’s disease Hodgkin’s lymphoma Burkitt’s lymphoma Nasopharyngeal carcinoma 



Research in my laboratory is supported by Cancer Research Switzerland (KFS-4091-02-2017), KFSP-PrecisionMS of the University of Zurich, the Vontobel Foundation, the Baugarten Foundation, the Sobek Foundation, the Swiss Vaccine Research Institute, the Swiss MS Society, Roche, ReiThera, and the Swiss National Science Foundation (310030B_182827 and CRSII5_180323).


  1. 1.
    Cesarman E (2014) Gammaherpesviruses and lymphoproliferative disorders. Annu Rev Pathol 9:349–372PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Oksenhendler E, Boutboul D, Galicier L (2019) Kaposi sarcoma-associated herpesvirus/human herpesvirus 8-associated lymphoproliferative disorders. Blood 133(11):1186–1190PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Kutok JL, Wang F (2006) Spectrum of Epstein-Barr virus-associated diseases. Annu Rev Pathol 1:375–404PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Mariggio G, Koch S, Schulz TF (2017) Kaposi sarcoma herpesvirus pathogenesis. Philos Trans R Soc Lond B Biol Sci 372(1732):20160275PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Münz C (2019) Latency and lytic replication in Epstein Barr virus associated oncogenesis. Nat Rev Microbiol 17(11):691–700PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Tugizov SM, Herrera R, Palefsky JM (2013) Epstein-Barr virus transcytosis through polarized oral epithelial cells. J Virol 87(14):8179–8194PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Murer A, McHugh D, Caduff N, Kalchschmidt JS, Barros MH, Zbinden A et al (2018) EBV persistence without its EBNA3A and 3C oncogenes in vivo. PLoS Pathog 14(4):e1007039PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Babcock GJ, Decker LL, Volk M, Thorley-Lawson DA (1998) EBV persistence in memory B cells in vivo. Immunity 9(3):395–404PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Sin SH, Dittmer DP (2013) Viral latency locus augments B-cell response in vivo to induce chronic marginal zone enlargement, plasma cell hyperplasia, and lymphoma. Blood 121(15):2952–2963PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Totonchy J, Cesarman E (2016) Does persistent HIV replication explain continued lymphoma incidence in the era of effective antiretroviral therapy? Curr Opin Virol 20:71–77PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Oksenhendler E, Carcelain G, Aoki Y, Boulanger E, Maillard A, Clauvel JP et al (2000) High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric castleman disease in HIV-infected patients. Blood 96(6):2069–2073PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Kalchschmidt JS, Bashford-Rogers R, Paschos K, Gillman AC, Styles CT, Kellam P et al (2016) Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in B cells. J Exp Med 213(6):921–928PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Totonchy J, Osborn JM, Chadburn A, Nabiee R, Argueta L, Mikita G et al (2018) KSHV induces immunoglobulin rearrangements in mature B lymphocytes. PLoS Pathog 14(4):e1006967PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Babcock JG, Hochberg D, Thorley-Lawson AD (2000) The expression pattern of Epstein-Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell. Immunity 13(4):497–506PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Laichalk LL, Thorley-Lawson DA (2005) Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo. J Virol 79(2):1296–1307PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Tugizov SM, Berline JW, Palefsky JM (2003) Epstein-Barr virus infection of polarized tongue and nasopharyngeal epithelial cells. Nat Med 9(3):307–314PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Gottschalk S, Rooney CM, Heslop HE (2005) Post-transplant lymphoproliferative disorders. Annu Rev Med 56:29–44PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Ong KW, Teo M, Lee V, Ong D, Lee A, Tan CS et al (2009) Expression of EBV latent antigens, mammalian target of rapamycin, and tumor suppression genes in EBV-positive smooth muscle tumors: clinical and therapeutic implications. Clin Cancer Res 15(17):5350–5358PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Tsao SW, Tsang CM, Pang PS, Zhang G, Chen H, Lo KW (2012) The biology of EBV infection in human epithelial cells. Semin Cancer Biol 22(2):137–143PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Fox CP, Shannon-Lowe C, Rowe M (2011) Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations. Herpesviridae 2:8PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Rose TM, Bruce AG, Barcy S, Fitzgibbon M, Matsumoto LR, Ikoma M et al (2018) Quantitative RNAseq analysis of Ugandan KS tumors reveals KSHV gene expression dominated by transcription from the LTd downstream latency promoter. PLoS Pathog 14(12):e1007441PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Tso FY, Kossenkov AV, Lidenge SJ, Ngalamika O, Ngowi JR, Mwaiselage J et al (2018) RNA-Seq of Kaposi’s sarcoma reveals alterations in glucose and lipid metabolism. PLoS Pathog 14(1):e1006844PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Parravicini C, Chandran B, Corbellino M, Berti E, Paulli M, Moore PS et al (2000) Differential viral protein expression in Kaposi’s sarcoma-associated herpesvirus-infected diseases: Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. Am J Pathol 156(3):743–749PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Jenner RG, Alba MM, Boshoff C, Kellam P (2001) Kaposi’s sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J Virol 75(2):891–902PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    McHugh D, Caduff N, Barros MHM, Rämer P, Raykova A, Murer A et al (2017) Persistent KSHV infection increases EBV-associated tumor formation in vivo via enhanced EBV lytic gene expression. Cell Host Microbe 22(1):61–73PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Mesri EA, Cesarman E, Boshoff C (2010) Kaposi’s sarcoma and its associated herpesvirus. Nat Rev Cancer 10(10):707–719PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Sin SH, Kim Y, Eason A, Dittmer DP (2015) KSHV latency locus cooperates with Myc to drive lymphoma in mice. PLoS Pathog 11(9):e1005135PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Ballon G, Chen K, Perez R, Tam W, Cesarman E (2011) Kaposi sarcoma herpesvirus (KSHV) vFLIP oncoprotein induces B cell transdifferentiation and tumorigenesis in mice. J Clin Invest 121(3):1141–1153PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Wilson JB, Bell JL, Levine AJ (1996) Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice. EMBO J 15(12):3117–3126PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Kulwichit W, Edwards RH, Davenport EM, Baskar JF, Godfrey V, Raab-Traub N (1998) Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice. Proc Natl Acad Sci U S A 95(20):11963–11968PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Kempkes B, Ling PD (2015) EBNA2 and its coactivator EBNA-LP. Curr Top Microbiol Immunol 391:35–59PubMedPubMedCentralGoogle Scholar
  32. 32.
    Kieser A, Sterz KR (2015) The latent membrane protein 1 (LMP1). Curr Top Microbiol Immunol 391:119–149PubMedPubMedCentralGoogle Scholar
  33. 33.
    Thorley-Lawson DA, Allday MJ (2008) The curious case of the tumour virus: 50 years of Burkitt’s lymphoma. Nat Rev Microbiol 6(12):913–924PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    AlQarni S, Al-Sheikh Y, Campbell D, Drotar M, Hannigan A, Boyle S et al (2018) Lymphomas driven by Epstein-Barr virus nuclear antigen-1 (EBNA1) are dependant upon Mdm2. Oncogene 37:3998PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Bubman D, Guasparri I, Cesarman E (2007) Deregulation of c-Myc in primary effusion lymphoma by Kaposi’s sarcoma herpesvirus latency-associated nuclear antigen. Oncogene 26(34):4979–4986PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Liu J, Martin HJ, Liao G, Hayward SD (2007) The Kaposi’s sarcoma-associated herpesvirus LANA protein stabilizes and activates c-Myc. J Virol 81(19):10451–10459PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Chaudhary PM, Jasmin A, Eby MT, Hood L (1999) Modulation of the NF-kappa B pathway by virally encoded death effector domains-containing proteins. Oncogene 18(42):5738–5746PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Sun Q, Zachariah S, Chaudhary PM (2003) The human herpes virus 8-encoded viral FLICE-inhibitory protein induces cellular transformation via NF-kappaB activation. J Biol Chem 278(52):52437–52445PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Paschos K, Parker GA, Watanatanasup E, White RE, Allday MJ (2012) BIM promoter directly targeted by EBNA3C in polycomb-mediated repression by EBV. Nucleic Acids Res 40(15):7233–7246PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Skalska L, White RE, Parker GA, Turro E, Sinclair AJ, Paschos K et al (2013) Induction of p16(INK4a) is the major barrier to proliferation when Epstein-Barr virus (EBV) transforms primary B cells into lymphoblastoid cell lines. PLoS Pathog 9(2):e1003187PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Cen O, Longnecker R (2015) Latent membrane protein 2 (LMP2). Curr Top Microbiol Immunol 391:151–180PubMedPubMedCentralGoogle Scholar
  42. 42.
    Platt G, Carbone A, Mittnacht S (2002) p16INK4a loss and sensitivity in KSHV associated primary effusion lymphoma. Oncogene 21(12):1823–1831PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Klein U, Gloghini A, Gaidano G, Chadburn A, Cesarman E, Dalla-Favera R et al (2003) Gene expression profile analysis of AIDS-related primary effusion lymphoma (PEL) suggests a plasmablastic derivation and identifies PEL-specific transcripts. Blood 101(10):4115–4121PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Jenner RG, Maillard K, Cattini N, Weiss RA, Boshoff C, Wooster R et al (2003) Kaposi’s sarcoma-associated herpesvirus-infected primary effusion lymphoma has a plasma cell gene expression profile. Proc Natl Acad Sci U S A 100(18):10399–10404PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Farrell PJ (2019) Epstein-Barr virus and cancer. Annu Rev Pathol 14:29–53PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Cesarman E, Damania B, Krown SE, Martin J, Bower M, Whitby D (2019) Kaposi sarcoma. Nat Rev Dis Primers 5(1):9PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    White RE, Ramer PC, Naresh KN, Meixlsperger S, Pinaud L, Rooney C et al (2012) EBNA3B-deficient EBV promotes B cell lymphomagenesis in humanized mice and is found in human tumors. J Clin Invest 122(4):1487–1502PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Arvey A, Ojesina AI, Pedamallu CS, Ballon G, Jung J, Duke F et al (2015) The tumor virus landscape of AIDS-related lymphomas. Blood 125(20):e14–e22PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Walens A, DiMarco AV, Lupo R, Kroger BR, Damrauer JS, Alvarez JV (2019) CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors. Elife 8:e43653PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Luttichau HR, Johnsen AH, Jurlander J, Rosenkilde MM, Schwartz TW (2007) Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3. J Biol Chem 282(24):17794–17805PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Herbst H, Foss HD, Samol J, Araujo I, Klotzbach H, Krause H et al (1996) Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin’s disease. Blood 87(7):2918–2929PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Sarris AH, Kliche KO, Pethambaram P, Preti A, Tucker S, Jackow C et al (1999) Interleukin-10 levels are often elevated in serum of adults with Hodgkin’s disease and are associated with inferior failure-free survival. Ann Oncol 10(4):433–440PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Lurain K, Polizzotto MN, Aleman K, Bhutani M, Wyvill KM, Goncalves PH et al (2019) Viral, immunologic, and clinical features of primary effusion lymphoma. Blood 133(16):1753–1761PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Bejarano MT, Masucci MG (1998) Interleukin-10 abrogates the inhibition of Epstein-Barr virus-induced B-cell transformation by memory T-cell responses. Blood 92(11):4256–4262PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Jochum S, Moosmann A, Lang S, Hammerschmidt W, Zeidler R (2012) The EBV immunoevasins vIL-10 and BNLF2a protect newly infected B cells from immune recognition and elimination. PLoS Pathog 8(5):e1002704PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Hsu SM, Lin J, Xie SS, Hsu PL, Rich S (1993) Abundant expression of transforming growth factor-beta 1 and -beta 2 by Hodgkin’s Reed-Sternberg cells and by reactive T lymphocytes in Hodgkin’s disease. Hum Pathol 24(3):249–255PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Tan GW, Visser L, Tan LP, van den Berg A, Diepstra A (2018) The microenvironment in Epstein-Barr virus-associated malignancies. Pathogens 7(2):E40PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Albanese M, Tagawa T, Bouvet M, Maliqi L, Lutter D, Hoser J et al (2016) Epstein-Barr virus microRNAs reduce immune surveillance by virus-specific CD8+ T cells. Proc Natl Acad Sci U S A 113(42):E6467–E6E75PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Murer A, Ruhl J, Zbinden A, Capaul R, Hammerschmidt W, Chijioke O et al (2019) MicroRNAs of Epstein-Barr virus attenuate T-cell-mediated immune control in vivo. MBio 10(1):e01941-18PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J et al (2004) Identification of virus-encoded microRNAs. Science 304(5671):734–736PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Xia T, O’Hara A, Araujo I, Barreto J, Carvalho E, Sapucaia JB et al (2008) EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3. Cancer Res 68(5):1436–1442PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Coscoy L, Ganem D (2000) Kaposi’s sarcoma-associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis. Proc Natl Acad Sci U S A 97(14):8051–8056PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Ressing ME, van Gent M, Gram AM, Hooykaas MJ, Piersma SJ, Wiertz EJ (2015) Immune evasion by Epstein-Barr virus. Curr Top Microbiol Immunol 391:355–381PubMedPubMedCentralGoogle Scholar
  64. 64.
    Gujer C, Murer A, Muller A, Vanoaica D, Sutter K, Jacque E et al (2019) Plasmacytoid dendritic cells respond to Epstein-Barr virus infection with a distinct type I interferon subtype profile. Blood Adv 3(7):1129–1144PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Ma SD, Hegde S, Young KH, Sullivan R, Rajesh D, Zhou Y et al (2011) A new model of Epstein-Barr virus infection reveals an important role for early lytic viral protein expression in the development of lymphomas. J Virol 85(1):165–177PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Antsiferova O, Müller A, Rämer P, Chijioke O, Chatterjee B, Raykova A et al (2014) Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice. PLoS Pathog 10(8):e1004333PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Bristol JA, Djavadian R, Albright ER, Coleman CB, Ohashi M, Hayes M et al (2018) A cancer-associated Epstein-Barr virus BZLF1 promoter variant enhances lytic infection. PLoS Pathog 14(7):e1007179PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Correia S, Bridges R, Wegner F, Venturini C, Palser A, Middeldorp JM et al (2018) Sequence variation of Epstein-Barr virus: viral types, geography, codon usage, and diseases. J Virol 92(22):e01132-18PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Okuno Y, Murata T, Sato Y, Muramatsu H, Ito Y, Watanabe T et al (2019) Defective Epstein-Barr virus in chronic active infection and haematological malignancy. Nat Microbiol 4(3):404–413PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Uldrick TS, Polizzotto MN, Aleman K, O’Mahony D, Wyvill KM, Wang V et al (2011) High-dose zidovudine plus valganciclovir for Kaposi sarcoma herpesvirus-associated multicentric Castleman disease: a pilot study of virus-activated cytotoxic therapy. Blood 117(26):6977–6986PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Martin DF, Kuppermann BD, Wolitz RA, Palestine AG, Li H, Robinson CA (1999) Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. Roche Ganciclovir Study Group. N Engl J Med 340(14):1063–1070PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Robles R, Lugo D, Gee L, Jacobson MA (1999) Effect of antiviral drugs used to treat cytomegalovirus end-organ disease on subsequent course of previously diagnosed Kaposi’s sarcoma in patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 20(1):34–38PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Marquet J, Velazquez-Kennedy K, Lopez S, Benito A, Blanchard MJ, Garcia-Vela JA (2018) Case report of a primary effusion lymphoma successfully treated with oral valganciclovir after failing chemotherapy. Hematol Oncol 36(1):316–319PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Casagrande N, Borghese C, Visser L, Mongiat M, Colombatti A, Aldinucci D (2019) CCR5 antagonism by maraviroc inhibits Hodgkin lymphoma microenvironment interactions and xenograft growth. Haematologica 104(3):564–575PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Uldrick TS, Wyvill KM, Kumar P, O’Mahony D, Bernstein W, Aleman K et al (2012) Phase II study of bevacizumab in patients with HIV-associated Kaposi’s sarcoma receiving antiretroviral therapy. J Clin Oncol 30(13):1476–1483PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Laubach J, Richardson P, Anderson K (2011) Multiple myeloma. Annu Rev Med 62:249–264PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Siddiqi T, Joyce RM (2008) A case of HIV-negative primary effusion lymphoma treated with bortezomib, pegylated liposomal doxorubicin, and rituximab. Clin Lymphoma Myeloma 8(5):300–304PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Muzes G, Sipos F, Csomor J, Sreter L (2013) Successful tocilizumab treatment in a patient with human herpesvirus 8-positive and human immunodeficiency virus-negative multicentric Castleman’s disease of plasma cell type nonresponsive to rituximab-CVP therapy. APMIS 121(7):668–674PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Nagao A, Nakazawa S, Hanabusa H (2014) Short-term efficacy of the IL6 receptor antibody tocilizumab in patients with HIV-associated multicentric Castleman disease: report of two cases. J Hematol Oncol 7:10PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Linnerbauer S, Behrends U, Adhikary D, Witter K, Bornkamm GW, Mautner J (2014) Virus and autoantigen-specific CD4+ T cells are key effectors in a SCID mouse model of EBV-associated post-transplant lymphoproliferative disorders. PLoS Pathog 10(5):e1004068PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    van Zyl DG, Tsai MH, Shumilov A, Schneidt V, Poirey R, Schlehe B et al (2018) Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. PLoS Pathog 14(12):e1007464PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Viral Immunobiology, Institute of Experimental ImmunologyUniversity of ZürichZürichSwitzerland

Personalised recommendations