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Epstein–Barr virus infection in humans: from harmless to life endangering virus–lymphocyte interactions

Abstract

After the primary infection, that may or may not cause infectious mononucleosis, the ubiquitous Epstein–Barr virus (EBV) is carried for lifetime. The great majority of adult humans are virus carriers. EBV was discovered in a B-cell lymphoma (Burkitt lymphoma). EBV infection in humans is the example for the power of immune surveillance against virus transformed, potentially malignant cells. Although the virus can transform B lymphocytes in vitro into proliferating lines, it induces malignancy directly only in immunosuppressed hosts. EBV-induced growth transformation occurs only in B lymphocytes. It is the result of a complex interaction between virally encoded and cellular proteins. Different forms of the virus–cell and the cell–host interactions have evolved during a long period of coexistence between the virus and all Old World (but not New World) primates. The asymptomatic carrier state is based on a viral-strategy that downregulates the expression of the transforming proteins in the virus-carrying cell. In addition to the silent viral-gene carriers and the expressors of the nine virus-encoded genes that drive the growth program, virus carrying cells exist that show other patterns of gene expression, depending on the differentiated state of the host cell. Certain combinations contribute to malignant transformation, but only in conjunction with additional cellular changes. These are induced by direct or cytokine-mediated interactions with normal cells of the immune system.

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References

  • Abbot SD, Rowe M, Cadwallader K, Ricksten A, Gordon J, Wang F et al. (1990). Epstein–Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein. J Virol 64: 2126–2134.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Altiok E, Minarovits J, Hu LF, Contreras-Brodin B, Klein G, Ernberg I . (1992). Host-cell-phenotype-dependent control of the BCR2/BWR1 promoter complex regulates the expression of Epstein–Barr virus nuclear antigens 2–6 [published erratum appears in Proc Natl Acad Sci USA 1992; 89: 6225]. Proc Natl Acad Sci USA 89: 905–909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Atayar C, Poppema S, Visser L, van den Berg A . (2006). Cytokine gene expression profile distinguishes CD4+/CD57+ T cells of the nodular lymphocyte predominance type of Hodgkin's lymphoma from their tonsillar counterparts. J Pathol 208: 423–430.

    Article  CAS  PubMed  Google Scholar 

  • Babcock GJ, Decker LL, Volk M, Thorley-Lawson DA . (1998). EBV persistence in memory B cells in vivo. Immunity 9: 395–404.

    Article  CAS  PubMed  Google Scholar 

  • Bandobashi K, Liu A, Nagy N, Kis LL, Nishikawa J, Bjorkholm M et al. (2005). EBV infection induces expression of the transcription factors ATF-2/c-Jun in B lymphocytes but not in B-CLL cells. Virus Genes 30: 323–330.

    Article  CAS  PubMed  Google Scholar 

  • Baumforth KR, Flavell JR, Reynolds GM, Davies G, Pettit TR, Wei W et al. (2005). Induction of autotaxin by the Epstein–Barr virus promotes the growth and survival of Hodgkin lymphoma cells. Blood 106: 2138–2146.

    Article  CAS  PubMed  Google Scholar 

  • Bargou RC, Emmerich F, Krappmann D, Bommert K, Mapara MY, Arnold W et al. (1997). Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells. J Clin Invest 100: 2961–2969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bechtel D, Kurth J, Unkel C, Kuppers R . (2005). Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas. Blood 106: 4345–4350.

    Article  CAS  PubMed  Google Scholar 

  • Cabannes E, Khan G, Aillet F, Jarrett RF, Hay RT . (1999). Mutations in the IkBa gene in Hodgkin's disease suggest a tumour suppressor role for IkappaBalpha. Oncogene 18: 3063–3070.

    Article  CAS  PubMed  Google Scholar 

  • Caligaris-Cappio F, Hamblin TJ . (1999). B-cell chronic lymphocytic leukemia: a bird of a different feather. J Clin Oncol 17: 399–408.

    Article  CAS  PubMed  Google Scholar 

  • Carbone A, Gloghini A, Gruss HJ, Pinto A . (1995). CD40 ligand is constitutively expressed in a subset of T cell lymphomas and on the microenvironmental reactive T cells of follicular lymphomas and Hodgkin's disease. Am J Pathol 147: 912–922.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen F, Zou JZ, di Renzo L, Winberg G, Hu LF, Klein E et al. (1995). A subpopulation of normal B cells latently infected with Epstein–Barr virus resembles Burkitt lymphoma cells in expressing EBNA-1 but not EBNA-2 or LMP1. J Virol 69: 3752–3758.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chiang AK, Tao Q, Srivastava G, Ho FC . (1996). Nasal NK- and T-cell lymphomas share the same type of Epstein–Barr virus latency as nasopharyngeal carcinoma and Hodgkin's disease. Int J Cancer 68: 285–290.

    Article  CAS  PubMed  Google Scholar 

  • Contreras-Brodin B, Karlsson A, Nilsson T, Rymo L, Klein G . (1996). B cell-specific activation of the Epstein–Barr virus-encoded C promoter compared with the wide-range activation of the W promoter. J Gen Virol 77: 1159–1162.

    Article  CAS  PubMed  Google Scholar 

  • Contreras-Brodin BA, Anvret M, Imreh S, Altiok E, Klein G, Masucci MG . (1991). B cell phenotype-dependent expression of the Epstein–Barr virus nuclear antigens EBNA-2 to EBNA-6: studies with somatic cell hybrids. J Gen Virol 72: 3025–3033.

    Article  CAS  PubMed  Google Scholar 

  • Chaganti S, Bell AI, Pastor NB, Milner AE, Drayson M, Gordon J et al. (2005). Epstein–Barr virus infection in vitro can rescue germinal center B cells with inactivated immunoglobulin genes. Blood 106: 4249–4252.

    Article  CAS  PubMed  Google Scholar 

  • Deacon EM, Pallesen G, Niedobitek G, Crocker J, Brooks L, Rickinson AB et al. (1993). Epstein–Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells. J Exp Med 177: 339–349.

    Article  CAS  PubMed  Google Scholar 

  • Doyle MG, Catovsky D, Crawford DH . (1993). Infection of leukaemic B lymphocytes by Epstein–Barr virus. Leukemia 7: 1858–1864.

    CAS  PubMed  Google Scholar 

  • Dukers DF, Meij P, Vervoort MB, Vos W, Scheper RJ, Meijer CJ et al. (2000). Direct immunosuppressive effects of EBV-encoded latent membrane protein 1. J Immunol 165: 663–670.

    Article  CAS  PubMed  Google Scholar 

  • Epstein MA, Achong BG, Barr YM. . (1964). Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet 15: 702–703.

    Article  Google Scholar 

  • Fahraeus R, Fu HL, Ernberg I, Finke J, Rowe M, Klein G et al. (1988). Expression of Epstein–Barr virus-encoded proteins in nasopharyngeal carcinoma. Int J Cancer 42: 329–338.

    Article  CAS  PubMed  Google Scholar 

  • Fahraeus R, Jansson A, Ricksten A, Sjöblom A, Rymo L . (1990). Epstein–Barr virus-encoded nuclear antigen 2 activates the viral latent membrane protein promoter by modulating the activity of a negative regulatory element. Proc Natl Acad Sci USA 87: 7390–7394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Falk K, Linde A, Johnson D, Lennette E, Ernberg I, Lundkvist A . (1995). Synthetic peptides deduced from the amino acid sequence of Epstein–Barr virus nuclear antigen 6 (EBNA 6): antigenic properties, production of monoreactive reagents, and analysis of antibody responses in man. J Med Virol 46: 349–357.

    Article  CAS  PubMed  Google Scholar 

  • Frisan T, Sjoberg J, Dolcetti R, Boiocchi M, De Re V, Carbone A et al. (1995). Local suppression of Epstein–Barr virus (EBV)-specific cytotoxicity in biopsies of EBV-positive Hodgkin's disease. Blood 86: 1493–1501.

    CAS  PubMed  Google Scholar 

  • Hammerschmidt W, Sugden B . (1989). Genetic analysis of immortalizing functions of Epstein–Barr virus in human B lymphocytes. Nature 340: 393–397.

    Article  CAS  PubMed  Google Scholar 

  • Harabuchi Y, Yamanaka N, Kataura A, Imai S, Kinoshita T, Mizuno F et al. (1990). Epstein–Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma. Lancet 335: 128–130.

    Article  CAS  PubMed  Google Scholar 

  • Henle W, Henle G, Lennette ET . (1979). The Epstein–Barr virus. Sci Am 241: 48–59.

    Article  CAS  PubMed  Google Scholar 

  • Hertel CB, Zhou XG, Hamilton-Dutoit SJ, Junker S . (2002). Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma. Oncogene 21: 4908–4920.

    Article  CAS  PubMed  Google Scholar 

  • Hjalgrim H, Askling J, Rostgaard K, Hamilton-Dutoit S, Frisch M, Zhang JS et al. (2003). Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med 349: 1324–1332.

    Article  CAS  PubMed  Google Scholar 

  • Hochberg D, Middeldorp JM, Catalina M, Sullivan JL, Luzuriaga K, Thorley-Lawson DA . (2004). Demonstration of the Burkitt's lymphoma Epstein–Barr virus phenotype in dividing latently infected memory cells in vivo. Proc Natl Acad Sci USA 101: 239–244.

    Article  CAS  PubMed  Google Scholar 

  • Horie R, Watanabe T, Morishita Y, Ito K, Ishida T, Kanegae Y et al. (2002). Ligand-independent signaling by overexpressed CD30 drives NF-kappaB activation in Hodgkin–Reed-Sternberg cells. Oncogene 21: 2493–2503.

    Article  CAS  PubMed  Google Scholar 

  • Ishida T, Ishii T, Inagaki A, Yano H, Komatsu H, Iida S et al. (2006). Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res 66: 5716–5722.

    Article  CAS  PubMed  Google Scholar 

  • Kanzler H, Kuppers R, Hansmann ML, Rajewsky K . (1996). Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J Exp Med 184: 1495–1505.

    Article  CAS  PubMed  Google Scholar 

  • Kanzler H, Kuppers R, Helmes S, Wacker HH, Chott A, Hansmann ML et al. (2000). Hodgkin and Reed-Sternberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones: potential precursors of Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Blood 95: 1023–1031.

    CAS  PubMed  Google Scholar 

  • Kennedy G, Komano J, Sugden B . (2003). Epstein–Barr virus provides a survival factor to Burkitt's lymphomas. Proc Natl Acad Sci USA 100: 14269–14274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kis LL, Nishikawa J, Takahara M, Nagy N, Matskova L, Takada K et al. (2005). In vitro EBV-infected subline of KMH2, derived from Hodgkin lymphoma, expresses only EBNA-1, while CD40 ligand and IL-4 induce LMP-1 but not EBNA-2. Int J Cancer 113: 937–945.

    Article  CAS  PubMed  Google Scholar 

  • Kis LL, Takahara M, Nagy N, Klein G, Klein E . (2006a). IL-10 can induce the expression of EBV-encoded latent membrane protein-1 (LMP-1) in the absence of EBNA-2 in B lymphocytes and in Burkitt lymphoma- and NK lymphoma-derived cell lines. Blood 107: 2928–2935.

    Article  CAS  PubMed  Google Scholar 

  • Kis LL, Takahara M, Nagy N, Klein G, Klein E . (2006b). Cytokine mediated induction of the major Epstein–Barr virus (EBV)-encoded transforming protein, LMP-1. Immunol Lett 104: 83–88.

    Article  CAS  PubMed  Google Scholar 

  • Klein G . (1994). Epstein–Barr virus strategy in normal and neoplastic B cells. Cell 77: 791–793.

    Article  CAS  PubMed  Google Scholar 

  • Komano J, Maruo S, Kurozumi K, Oda T, Takada K . (1999). Oncogenic role of Epstein–Barr virus-encoded RNAs in Burkitt's lymphoma cell line Akata. J Virol 73: 9827–9831.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kuppers R . (2002). Molecular biology of Hodgkin's lymphoma. Adv Cancer Res 84: 277–312.

    Article  PubMed  Google Scholar 

  • Kuppers R, Rajewsky K, Zhao M, Simons G, Laumann R, Fischer R et al. (1994). Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci USA 91: 10962–10966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurth J, Hansmann ML, Rajewsky K, Kuppers R . (2003). Epstein–Barr virus-infected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction. Proc Natl Acad Sci USA 100: 4730–4735.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurth J, Spieker T, Wustrow J, Strickler GJ, Hansmann LM, Rajewsky K et al. (2000). EBV-infected B cells in infectious mononucleosis: viral strategies for spreading in the B cell compartment and establishing latency. Immunity 13: 485–495.

    Article  CAS  PubMed  Google Scholar 

  • Lennette ET, Rymo L, Yadav M, Masucci G, Merk K, Timar L et al. (1993). Disease-related differences in antibody patterns against EBV-encoded nuclear antigens EBNA 1, EBNA 2 and EBNA 6. Eur J Cancer 29A: 1584–1589.

    Article  CAS  PubMed  Google Scholar 

  • Levitskaya J, Coram M, Levitsky V, Imreh S, Steigerwald-Mullen PM, Klein G et al. (1995). Inhibition of antigen processing by the internal repeat region of the Epstein–Barr virus nuclear antigen-1. Nature 375: 685–688.

    Article  CAS  PubMed  Google Scholar 

  • Lewin N, Minarovits J, Weber G, Ehlin-Henriksson B, Wen T, Mellstedt H et al. (1991). Clonality and methylation status of the Epstein–Barr virus (EBV) genomes in in vivo-infected EBV-carrying chronic lymphocytic leukemia (CLL) cell lines. Int J Cancer 48: 62–66.

    Article  CAS  PubMed  Google Scholar 

  • Maeda A, Bandobashi K, Nagy N, Teramoto N, Gogolak P, Pokrovskaja K et al. (2001). Epstein–Barr virus can infect B-chronic lymphocytic leukemia cells but it does not orchestrate the cell cycle regulatory proteins. J Hum Virol 4: 227–237.

    CAS  PubMed  Google Scholar 

  • Mancao C, Altmann M, Jungnickel B, Hammerschmidt W . (2005). Rescue of ‘crippled’ germinal center B cells from apoptosis by Epstein–Barr virus. Blood 106: 4339–4344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marshall NA, Christie LE, Munro LR, Culligan DJ, Johnston PW, Barker RN et al. (2004). Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood 103: 1755–1762.

    Article  CAS  PubMed  Google Scholar 

  • Martin-Subero JI, Gesk S, Harder L, Sonoki T, Tucker PW, Schlegelberger B et al. (2002). Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma. Blood 99: 1474–1477.

    Article  CAS  PubMed  Google Scholar 

  • Nakayama T, Hieshima K, Nagakubo D, Sato E, Nakayama M, Kawa K et al. (2004). Selective induction of Th2-attracting chemokines CCL17 and CCL22 in human B cells by latent membrane protein 1 of Epstein–Barr virus. J Virol 78: 1665–1674.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nilsson K, Ponten J . (1975). Classification and biological nature of established human hematopoietic cell lines. Int J Cancer 15: 321–341.

    Article  CAS  PubMed  Google Scholar 

  • Oudejans JJ, Jiwa M, van den Brule AJ, Grasser FA, Horstman A, Vos W et al. (1995). Detection of heterogeneous Epstein–Barr virus gene expression patterns within individual post-transplantation lymphoproliferative disorders. Am J Pathol 147: 923–933.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pallesen G, Hamilton-Dutoit SJ, Rowe M, Young LS . (1991). Expression of Epstein–Barr virus latent gene products in tumour cells of Hodgkin's disease. Lancet 337: 320–322.

    Article  CAS  PubMed  Google Scholar 

  • Pope JH, Horne MK, Scott W . (1968). Transformation of foetal human leukocytes in vitro by filtrates of a human leukaemic cell line containing herpes-like virus. Int J Cancer 3: 857–866.

    Article  CAS  PubMed  Google Scholar 

  • Rickinson AB, Finerty S, Epstein MA . (1982). Interaction of Epstein–Barr virus with leukaemic B cells in vitro. I. Abortive infection and rare cell line establishment from chronic lymphocytic leukaemic cells. Clin Exp Immunol 50: 347–354.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rickinson AB, Kieff E . (2001). Epstein–Barr virus. In: Knipe DM and Howley PM (eds). Fields Virology, 4th edn. Vol. 2. Lippincott Williams and Wilkins: Philadelphia, pp 2575–2628.

    Google Scholar 

  • Roschke V, Kopantzev E, Dertzbaugh M, Rudikoff S . (1997). Chromosomal translocations deregulating c-myc are associated with normal immune responses. Oncogene 14: 3011–3016.

    Article  CAS  PubMed  Google Scholar 

  • Rowe M, Lear AL, Croom-Carter D, Davies AH, Rickinson AB . (1992). Three pathways of Epstein–Barr virus gene activation from EBNA1-positive latency in B lymphocytes. J Virol 66: 122–131.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rowe M, Rowe DT, Gregory CD, Young LS, Farrell PJ, Rupani H et al. (1987). Differences in B cell growth phenotype reflect novel patterns of Epstein–Barr virus latent gene expression in Burkitt's lymphoma cells. EMBO J 6: 2743–2751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schaefer BC, Strominger JL, Speck SH . (1995). Redefining the Epstein–Barr virus-encoded nuclear antigen EBNA-1 gene promoter and transcription initiation site in group I Burkitt lymphoma cell lines. Proc Natl Acad Sci USA 92: 10565–10569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwering I, Brauninger A, Klein U, Jungnickel B, Tinguely M, Diehl V et al. (2003). Loss of the B-lineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood 101: 1505–1512.

    Article  CAS  PubMed  Google Scholar 

  • Staratschek-Jox A, Wolf J, Diehl V . (2000). Hodgkin's disease. In: Masters JRW, Palsson BO (eds). Human Cell Culture. Vol. 3. Kluwer Academic Publishers: Dordrecht, pp 339–353.

    Google Scholar 

  • Takada K, Yamamoto K, Osato T . (1980). Analysis of the transformation of human lymphocytes by Epstein–Barr virus. II. Abortive response of leukemic cells to the transforming virus. Intervirology 13: 223–231.

    Article  CAS  PubMed  Google Scholar 

  • Takahara M, Kis LL, Nagy N, Liu A, Harabuchi Y, Klein G et al. (2006). Concomitant increase of LMP1 and CD25 (IL-2-receptor alpha) expression induced by IL-10 in the EBV-positive NK lines SNK6 and KAI3. Int J Cancer 119: 2775–2783.

    Article  CAS  PubMed  Google Scholar 

  • Teramoto N, Gogolak P, Nagy N, Maeda A, Kvarnung K, Bjorkholm M et al. (2000). Epstein–Barr virus-infected B-chronic lymphocyte leukemia cells express the virally encoded nuclear proteins but they do not enter the cell cycle. J Hum Virol 3: 125–136.

    CAS  PubMed  Google Scholar 

  • Tierney R, Kirby H, Nagra J, Rickinson A, Bell A . (2000). The Epstein–Barr virus promoter initiating B-cell transformation is activated by RFX proteins and the B-cell-specific activator protein BSAP/Pax5. J Virol 74: 10458–10467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thorley-Lawson DA . (2001). Epstein–Barr virus: exploiting the immune system. Nat Rev Immunol 1: 75–82.

    Article  CAS  PubMed  Google Scholar 

  • Tomita Y, Avila-Carino J, Yamamoto K, Mellstedt H, Klein E . (1998). Recognition of B-CLL cells experimentally infected with EBV by autologous T lymphocytes. Immunol Lett 60: 73–79.

    Article  CAS  PubMed  Google Scholar 

  • Tsimberidou AM, Keating MJ, Bueso-Ramos CE, Kurzrock R . (2006). Epstein–Barr virus in patients with chronic lymphocytic leukemia: a pilot study. Leuk Lymphoma 47: 827–836.

    Article  PubMed  Google Scholar 

  • Tsuge I, Morishima T, Morita M, Kimura H, Kuzushima K, Matsuoka H . (1999). Characterization of Epstein–Barr virus (EBV)-infected natural killer (NK) cell proliferation in patients with severe mosquito allergy; establishment of an IL-2-dependent NK-like cell line. Clin Exp Immunol 115: 385–392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van den Berg A, Visser L, Poppema S . (1999). High expression of the CC chemokine TARC in Reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltration Hodgkin's lymphoma. Am J Pathol 154: 1685–1691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vockerodt M, Belge G, Kube D, Irsch J, Siebert R, Tesch H et al. (2002). An unbalanced translocation involving chromosome 14 is the probable cause for loss of potentially functional rearranged immunoglobulin heavy chain genes in the Epstein–Barr virus-positive Hodgkin's lymphoma-derived cell line L591. Br J Haematol 119: 640–646.

    Article  CAS  PubMed  Google Scholar 

  • Walls EV, Doyle MG, Patel KK, Allday MJ, Catovsky D, Crawford DH . (1989). Activation and immortalization of leukaemic B cells by Epstein–Barr virus. Int J Cancer 44: 846–853.

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Tsang SF, Kurilla MG, Cohen JI, Kieff E . (1990). Epstein–Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1. J Virol 64: 3407–3416.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Young L, Alfieri C, Hennessy K, Evans H, O'Hara C, Anderson KC et al. (1989). Expression of Epstein–Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med 321: 1080–1085.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Nagata H, Ikeuchi T, Mukai H, Oyoshi MK, Demachi A et al. (2003). Common cytological and cytogenetic features of Epstein–Barr virus (EBV)-positive natural killer (NK) cells and cell lines derived from patients with nasal T/NK-cell lymphomas, chronic active EBV infection and hydroa vacciniforme-like eruptions. Br J Haematol 121: 805–814.

    Article  PubMed  Google Scholar 

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Acknowledgements

Supported by funds from the Swedish Cancer Society, Sweden. LLK is recipient of Cancer Research Fellowship of Cancer Research Institute (New York)/Concern Foundation (Los Angeles).

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Klein, E., Kis, L. & Klein, G. Epstein–Barr virus infection in humans: from harmless to life endangering virus–lymphocyte interactions. Oncogene 26, 1297–1305 (2007). https://doi.org/10.1038/sj.onc.1210240

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