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29 - Effects on apoptosis, cell cycle and transformation, and comparative aspects of EBV with other DNA tumor viruses

from Part II - Basic virology and viral gene effects on host cell functions: gammaherpesviruses

Published online by Cambridge University Press:  24 December 2009

By
George Klein  and
Ingemar Ernberg
Edited by
Ann Arvin ,
Gabriella Campadelli-Fiume ,
Edward Mocarski ,
Patrick S. Moore ,
Bernard Roizman ,
Richard Whitley  and
Koichi Yamanishi
George Klein
Affiliation:
Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA USA
Ingemar Ernberg
Affiliation:
Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA USA
Ann Arvin
Affiliation:
Stanford University, California
Gabriella Campadelli-Fiume
Affiliation:
Università degli Studi, Bologna, Italy
Edward Mocarski
Affiliation:
Emory University, Atlanta
Patrick S. Moore
Affiliation:
University of Pittsburgh
Bernard Roizman
Affiliation:
University of Chicago
Richard Whitley
Affiliation:
University of Alabama, Birmingham
Koichi Yamanishi
Affiliation:
University of Osaka, Japan
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Summary

The list of human viruses presently known to cause or to contribute to tumor development comprise four DNA viruses, Epstein–Barr virus, certain human papilloma virus subtypes, hepatitis B virus, and Kaposi sarcoma herpesvirus (HHV-8); and two RNA viruses, adult T-cell leukemia virus (HTLV-1) and hepatitis virus C. In addition, while HIV infection is not directly tumorigenic, it increases the incidence of certain tumors.

The purpose of this chapter is to consider EBV and HHV-8 in relation to the known DNA tumor viruses, with particular focus on tumorigenicity.

Viral strategy at the molecular level as a tumor risk factor

Altered genes or environmental factors are usually considered as major risk factors for tumor development. However, the strategy of certain viruses may constitute a risk factor in itself. Tumor-associated viruses in humans have a survival strategy, like other viruses, aiming to maintain, replicate and propagate their genomes, but some features of this strategy entail a risk to initiate or favor tumor development under certain circumstances. This implies that only a small minority of the infected cells enter the pathway towards a malignant tumor and even fewer succeed.

Three types of virus–host cell interactions may carry a risk

  1. Blocking of late viral functions or blocking the replicative cycle, by mutation or deletion of genetic material, e.g., due to the integration of the viral genome, as exemplified by HPV or adenovirus transformation in vitro.

  2. Infection of cells that are not fully permissive for viral replication, for species or tissue specific reasons. Permissiveness for the early but not the late functions of the viral cycle is particularly dangerous. The early viral proteins may exert continuous proliferation stimulating and/or apoptosis preventing effects. Infection of hamster or guinea pig cells with some of the human adenoviruses and SV40 infection of rodent cells may serve as examples.

  3. […]

Type
Chapter
Information
Human Herpesviruses
Biology, Therapy, and Immunoprophylaxis
 , pp. 514 - 539
Publisher: Cambridge University Press
Print publication year: 2007

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References

Ambinder, R. F., Shah, W. A., Rawlins, D. R., Hayward, G. S., and Hayward, S. D. (1990). Definition of the sequence requirements for binding of the EBNA-1 protein to its palindromic target sites in Epstein–Barr virus DNA. J. Virol., 64, 2369–2379.Google ScholarPubMed
Aman, P., Rowe, M., Kai, C.et al. (1990). Effect of the EBNA-2 gene on the surface antigen phenotype of transfected EBV-negative B-lymphoma lines. Int. J. Cancer, 45, 77–82.CrossRefGoogle ScholarPubMed
Andersson-Anvret, M., Klein, G., Forsby, N., and Henle, W. (1978). The association between undifferentiated nasopharyngeal carcinoma and Epstein–Barr virus shown by correlated nucleic acid hybridization and histopathological studies. IARC Sci. Publ., 20, 347–357.Google Scholar
Amini, R. M., Enblad, G., Gustavsson, A.et al. (2000). Treatment outcome in patients younger than 60 years with advanced stages (IIB-IV) of Hodgkin's disease: the Swedish National Health Care Programme experience. Eur. J. Haematol., 65, 379–389.CrossRefGoogle ScholarPubMed
Axdorph, U., Porwit-MacDonald, , Sjoberg, A. J.et al. (1999). Epstein–Barr virus expression in Hodgkin's disease in relation to patient characteristics, serum factors and blood lymphocyte function. Br. J. Cancer, 81, 1182–1187.CrossRefGoogle ScholarPubMed
Baichwal, V. R., Hammerschmidt, W., and Sugden, B. (1989). Characterization of the BNLF-1 oncogene of Epstein–Barr virus. Curr. Top. Microbiol. Immunol., 144, 233–239.Google ScholarPubMed
Bittner, J. J. (1936). Some possible effects of nursing on the mammary tumor incidence in mice. Science, 84, 162–168.CrossRefGoogle ScholarPubMed
Bodescot, M. and Perricaudet, M. (1986). Epstein–Barr virus mRNAs produced by alternative splicing. Nucl. Acids Res., 14, 7103–7114.CrossRefGoogle ScholarPubMed
Bodescot, M., Perricaudet, M., and Farrell, P. J. (1987). A promoter for the highly spliced EBNA family of RNAs of Epstein–Barr virus. J. Virol., 61, 3424–3430.Google ScholarPubMed
Bornkamm, G. W. and Hammerschmidt, W. (2001). Molecular virology of Epstein–Barr virus. Phil. Trans. R. Soc. Lond. B Biol. Sci., 356, 437–459.CrossRefGoogle ScholarPubMed
Burkhardt, A. L., Bolen, J. B., Kieff, E., and Longnecker, R. (1992). An Epstein–Barr virus transformation-associated membrane protein interacts with src family tyrosine kinases. J. Virol., 66, 5161–5167.Google ScholarPubMed
Caldwell, R. G., Brown, R. C., and Longnecker, R. (2000). Epstein–Barr virus LMP2A-induced B-cell survival in two unique classes of EmuLMP2A transgenic mice. J. Virol., 74, 1101–1113.CrossRefGoogle ScholarPubMed
Chen, F., Hu, L. F., Ernberg, I., Klein, G., and Winberg, G. (1995a). A subpopulation of normal B cells latenly infected with Epstein–Barr virus resembles Burkitt lymphoma cells in expressing EBNA-1 but not EBNA-2 or LMP1. J. Virol., 69, 3752–3758.Google Scholar
Chen, F., Zou, J. Z., Renzo, L.et al. (1995b). 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.Google Scholar
Chen, F., Chen, L., Lindwall, C., Xu, D., and Ernberg, I. (2004). Epstein–Barr virus latent membrane 2A (LMP2A) down-regulates telomerase reverse transcriptase (hTERT) in epithelial cell lines. Int. J. Cancer.Google Scholar
Choi, J. K., Lee, B. S., Shim, S. N., Li, M., and Jung, J. U. (2000). Identification of the novel K15 gene at the rightmost end of the Kaposi's sarcoma-associated herpesvirus genome. J. Virol., 74, 436–446.CrossRefGoogle ScholarPubMed
Chung, P. J., Chang, Y. S., Liang, C. L., and Meng, C. L. (2002). Negative regulation of Epstein–Barr virus latent membrane protein 1-mediated functions by the bone morphogenetic protein receptor IA-binding protein, BRAM1. J. Biol. Chem., 277, 39850–39857.CrossRefGoogle ScholarPubMed
Cohen, J. I., Wang, F., Mannick, J., and Kieff, E. (1989). Epstein–Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. Proc. Natl Acad Sci. USA., 86, 9558–9562.CrossRefGoogle ScholarPubMed
Contreras-Salazar, B., Klein, G., and Masucci, M. G. (1989). Host cell-dependent regulation of growth transformation-associated Epstein–Barr virus antigens in somatic cell hybrids. J. Virol., 63, 2768–2772.Google ScholarPubMed
Damania, B., Choi, J. K., and Jung, J. U. (2000). Signaling activities of gammaherpesvirus membrane proteins. J. Virol., 74, 1593–1601.CrossRefGoogle ScholarPubMed
Devergne, O., Hatzivassiliou, E., Izumi, K. M.et al. (1996). Association of TRAF1, TRAF2, and TRAF3 with an Epstein–Barr virus LMP1 domain important for B-lymphocyte transformation: role in NF-kappaB activation. Mol. Cell Biol., 16, 7098–7108.CrossRefGoogle ScholarPubMed
Dillner, J., Kallin, B., Ehlin–Henriksson, B., Timar, L., and Klein, G. (1985). Characterization of a second Epstein–Barr virus-determined nuclear antigen associated with the BamHI WYH region of EBV DNA. Int. J. Cancer, 35, 359–366.CrossRefGoogle ScholarPubMed
Dillner, J., Kallin, B., Alexander, H.et al. (1986a). An Epstein–Barr virus (EBV) – determined nuclear antigen (EBNA5) partly encoded by the transformation-associated Bam WYH region of EBV DNA: preferential expression in lymphoblastoid cell lines. Proc. Natl Acad. Sci. USA, 83, 6641–6645.CrossRefGoogle Scholar
Dillner, J., Kallin, B., Ehlin-Henriksson, B.et al. (1986b). The Epstein–Barr virus determined nuclear antigen is composed of at least three different antigens. Int. J. Cancer, 37, 195–200.CrossRefGoogle Scholar
Dirmeier, U., Neuhierl, B., Kilger, E., Reisbach, G., Sandberg, M. L., and Hammerschmidt, W. (2003). Latent membrane protein 1 is critical for efficient growth transformation of human B cells by Epstein–Barr virus. Cancer Res., 63, 2982–2989.Google Scholar
Drouet, E., Brousset, P., Fares, F.et al. (1999). High Epstein–Barr virus serum load and elevated titers of anti-ZEBRA antibodies in patients with EBV-harboring tumor cells of Hodgkin's disease. J. Med. Virol., 57, 383–389.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
Dukers, D. F., Jaspars, L. H., Vos, W.et al. (2000). Quantitative immunohistochemical analysis of cytokine profiles in Epstein–Barr virus-positive and -negative cases of Hodgkin's disease. J. Pathol., 190, 143–149.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
Dykstra, M. L., Longnecker, R., and Pierce, S. K. (2001). Epstein–Barr virus coopts lipid rafts to block the signaling and antigen transport functions of the BCR. Immunity, 14, 57–67.CrossRefGoogle ScholarPubMed
Eliopoulos, A. G. and Young, L. S. (2001). LMP1 structure and signal transduction. Semin. Cancer Biol. Rev., 11, 435–444.CrossRefGoogle ScholarPubMed
Eliopoulos, A. G., Dawson, C. W., Mosialos, G.et al. (1996). CD40-induced growth inhibition in epithelial cells is mimicked by Epstein–Barr virus-encoded LMP1: involvement of TRAF3 as a common mediator. Oncogene, 13, 2243–2254.Google ScholarPubMed
Eliopoulos, A. G., Stack, M., Dawson, C. W.et al. (1997). Epstein–Barr virus-encoded LMP1 and CD40 mediate IL-6 production in epithelial cells via an NF-kappaB pathway involving TNF receptor-associated factors. Oncogene, 14, 2899–2916.CrossRefGoogle ScholarPubMed
Ernberg, I., Kallin, B., Dillner, J.et al. (1986). Lymphoblastoid cell lines and Burkitt-lymphoma-derived cell lines differ in the expression of a second Epstein–Barr virus encoded nuclear antigen. Int. J. Cancer, 38, 729–737.CrossRefGoogle ScholarPubMed
Enblad, G., Sundstrom, C., and Glimelius, B. (1993). Infiltration of eosinophils in Hodgkin's disease involved lymph nodes predicts prognosis. Hematol. Oncol., 11, 187–193.CrossRefGoogle ScholarPubMed
Fahraeus, R., Rymo, L., Rhim, J. S., and Klein, G. (1990). Morphological transformation of human keratinocytes expressing the LMP gene of Epstein–Barr virus. Nature, 345, 447–449.CrossRefGoogle ScholarPubMed
Foulds, L. (1958). The natural history of cancer. J. Chronic Dis., 8, 2–37.CrossRefGoogle ScholarPubMed
Friborg, J., Kong, W., Hottiger, M., and Nabel, G. (1999). P53 inhibition by the LANA protein of KSHV protects against cell death. Nature, 402, 889–894.CrossRefGoogle ScholarPubMed
Fruehling, S. and Longnecker, R. (1997). The immunoreceptor tyrosine-based activation motif of Epstein–Barr virus LMP2A is essential for blocking BCR-mediated signal transduction. Virology, 235, 241–251.CrossRefGoogle ScholarPubMed
Fruehling, S.., Dolwick, K. M., Kremmer, E., and Longnecker, R. (1998). Tyrosine 112 of latent membrane protein 2A is essential for protein tyrosine kinase loading and regulation of Epstein–Barr virus latency. J. Virol., 72, 7796–7806.Google ScholarPubMed
Furth, J., Buffett, R. F., Barasiewicz-Rodriguez, M., and Upton, A. C. (1956). Character of agent inducing leukemia in newborn mice. Proc. Soc. Exp. Biol. Med., 93, 165–172.CrossRefGoogle Scholar
Gallo, R. C., Kalyanaraman, V. S., Sarngadharan, M. G.et al. (1983). Association of the human type-C retrovirus with a subset of adult T-cell cancers. Cancer Res., 42, 3892–3899.Google Scholar
Geser, A. D., Thé, G., Lenoir, G.et al. (1982). Final case reporting from the Ugandan prospective study of the relationship between EBV and Burkitt's lymphoma. Int. J. Cancer, 29, 397–400.CrossRefGoogle ScholarPubMed
Gires, O., Zimber-Strobl, U., Gonnella, R.et al. (1997). Latent membrane protein 1 of Epstein–Barr virus mimics a constitutively active receptor molecule. EMBO J., 16, 6131–6140.CrossRef
Gires, O., Kohlhuber, F., Kilger, E.et al. (1999). Latent membrane protein 1 of Epstein–Barr virus interacts with JAK3 and activates STAT proteins. EMBO J., 18, 3064–3073.CrossRefGoogle ScholarPubMed
Glaser, S. L., Lin, R. J., Stewart, S. L.et al. (1997). Epstein–Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data. Int. J. Cancer, 70, 375–382.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Gratama, J. W., Oosterveer, M. A. P., Zwaan, F. E., Lepoutre, J., Klein, G., and Ernberg, I. (1988). Eradication of Epstein–Barr virus by allogeneic bone marrow transplanation: implications for sites of viral latency. Proc. Natl Acad. Sci. USA, 85, 8693–8696.CrossRefGoogle Scholar
Gross, L. (1951). Spontaneous leukemia developing in C3H mice following inoculation in infancy with AK leukemic extracts of AK embryos. Proc. Soc. Exp. Biol. Med., 76, 27–32.CrossRefGoogle Scholar
Hatzivassiliou, E. and Mosialos, G. (2002). Cellular signaling pathways engaged by the Epstein–Barr virus transforming protein LMP1. Front Biosci., 7, 319–329.CrossRefGoogle ScholarPubMed
Hamilton-Dutoit, S. J., Pallesen, G., Karkov, J., Skinhoj, P., Franzmann, M. B., and Pedersen, C. (1989). Identification of EBV-DNA in tumour cells of AIDS-related lymphomas by in-situ hybridisation. Lancet, 1, 554–562.CrossRefGoogle ScholarPubMed
Hamilton-Dutoit, S. J., Pallesen, G., Franzmann, M. B.et al. (1991). Histopathology, immunophenotype, and association with Epstein–Barr virus as demonstrated by in situ nucleic acid hybridization. Am. J. Pathol., 138, 149–163.Google ScholarPubMed
Henderson, S., Rowe, M., Gregory, C.et al. (1991). Induction of bcl-2 expression by Epstein–Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell, 65, 1107–1115.CrossRefGoogle ScholarPubMed
Hennessy, K. and Kieff, E. (1983). One of two Epstein–Barr virus nuclear antigens contains a glycine–alanine copolymer domain. Proc. Natl Acad. Sci. USA, 80, 5665–5669.CrossRefGoogle ScholarPubMed
Hennessy, K. and Kieff, E. (1985). Second nuclear protein is encoded by Epstein–Barr virus in latent infection. Science, 227, 1238–1240.CrossRefGoogle ScholarPubMed
Hennessy, K., Heller, M., Santen, V., and Kieff, E. (1983). Simple repeat array in Epstein–Barr virus DNA encodes part of the Epstein–Barr nuclear antigen. Science, 220, 1396–1398.CrossRefGoogle ScholarPubMed
Hennessy, K., Fennewald, S., Hummel, M., Cole, T., and Kieff, E. (1984). A membrane protein encoded by Epstein–Barr virus in latent growth-transforming infection. Proc. Natl Acad. Sci. USA, 81, 7207–7211.CrossRefGoogle Scholar
Hennessy, K., Fennewald, S., and Kieff, E. (1985). A third viral nuclear protein in lymphoblasts immortalized by Epstein–Barr virus. Proc. Natl Acad. Sci. USA, 82, 5944–5948.CrossRefGoogle ScholarPubMed
Hickabottom, M., Parker, G. A., Freemont, P., Crook, T., and Allday, M. J. (2002). Two nonconsensus sites in the Epstein–Barr virus oncoprotein EBNA3A cooperate to bind the co-repressor carboxyl-terminal-binding protein (CtBP). J. Biol. Chem., 277, 47197–47204.CrossRefGoogle Scholar
Higuchi, M., Izumi, K. M., and Kieff, E. (2001). Epstein–Barr virus latent-infection membrane proteins are palmitoylated and raft-associated: protein 1 binds to the cytoskeleton through TNF receptor cytoplasmic factors. Proc. Natl Acad. Sci. USA, 98, 4675–4680.CrossRefGoogle ScholarPubMed
Hsieh, J. J., Henkel, T., Salmon, P., Robey, E., Peterson, M. G., and Hayward, S. D. (1996). Truncated mammalian Notch1 activates CBF1/RBPJk-repressed genes by a mechanism resembling that of Epstein–Barr virus EBNA2. Mol. Cell Biol., 16, 952–959.CrossRefGoogle ScholarPubMed
Hu, L-F., Minarovits, J., Cao, S. L.et al. (1991). Variable expression of latent membrane protein in nasopharyngeal carcinoma can be related to methylation status of the Epstein–Barr virus BNLF-1 5′-flanking region. J. Virol., 65, 1558–1567.Google ScholarPubMed
Hu, L-F., Chen, F., Zheng, X.et al. (1993). Clonability and tumorigenicity of human epithelial cells expressing the EBV encoded membrane protein LMP1, Oncogene, 8, 1575–1583.Google ScholarPubMed
Hu, L-F., Chen, F., Zhen, Q.et al. (1995). Differences in the growth pattern and clinical course of EBV-LMP1 expressing and non-expressing nasopharyngeal carcinomas. Eur. J. Cancer, 31, 658–660.CrossRefGoogle Scholar
Hu, L. F., Troyansky, B., Zhang, X.et al. (2000). Differences in the immunogenicity of latent membrane protein 1 (LMP1) encoded by Epstein–Barr virus genomes derived from LMP1-positive and – negative nasopharyngeal carcinoma. Cancer Res., 60, 5589–5593.Google ScholarPubMed
Ikeda, M., Ikeda, A., Longan, L. C., and Longnecker, R. (2000). The Epstein–Barr virus latent membrane protein 2A PY motif recruits WW domain-containing ubiquitin-protein ligases. Virology, 268, 178–191.CrossRefGoogle ScholarPubMed
Ikeda, M., Ikeda, A., Longnecker, R. (2002). Lysine-independent ubiquitination of Epstein–Barr virus LMP2A. Virology, 75, 153–159.CrossRefGoogle Scholar
Ikeda, A., Caldwell, R. G., Longnecker, R., and Ikeda, M. (2003). Itchy, a Nedd4 ubiquitin ligase, downregulates latent membrane protein 2A activity in B-cell signaling. J. Virol., 77, 5529–5534.CrossRefGoogle ScholarPubMed
Jiang, W. Q., Wendel-Hansen, V., Lundkvist, A., Ringertz, N., Klein, G., and Rosen, A. (1991). Intranuclear distribution of Epstein–Barr virus-encoded nuclear antigens EBNA-1, -2, -3 and -5. J. Cell Sci., 99, 497–502.Google ScholarPubMed
Jochner, N., Eick, D., Zimber-Strobl, U., Pawlita, M., Bornkamm, G. W., and Kempkes, B. (1996). Epstein–Barr virus nuclear antigen 2 is a transcriptional suppressor of the immunoglobulin mu gene: implications for the expression of the translocated c-myc gene in Burkitt's lymphoma cells. EMBO J., 15, 375–382.Google Scholar
Johannsen, E., Koh, E., Mosialos, G., Tong, X., Kieff, E., and Grossman, S. R. (1995). Epstein–Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU. 1. J. Virol., 69, 253–262.Google Scholar
Johannsen, E., Miller, C. L., Grossman, S. R., and Kieff, E. (1996). EBNA-2 and EBNA-3C extensively and mutually exclusively associate with RBPJ kappa in Epstein–Barr virus-transformed B lymphocytes. J. Virol., 70, 4179–4183.Google Scholar
Jones, C. H., Hayward, S. D., and Rawlins, D. R. (1989). Interaction of the lymphocyte-derived Epstein–Barr virus nuclear antigen EBNA-1 with its DNA-binding sites. J. Virol., 63, 101–110.Google ScholarPubMed
Kaiser, C., Laux, G., Eick, D., Jochner, N., Bornkamm, G. W., and Kempkes, B. (1999). The proto-oncogene c-myc is a direct target gene of Epstein–Barr virus nuclear antigen 2. J. Virol., 73, 4481–4484.Google ScholarPubMed
Kanamori, M., Watanabe, S., Honma, R.et al. (2004). Epstein–Barr virus nuclear antigen leader protein induces expression of thymus – and activation-regulated chemokine in B cells. J. Virol., 78, 3984–3993.CrossRefGoogle ScholarPubMed
Kashuba, E., Pokrovskaja, K., Klein, G., and Szekely, L. (1999). Epstein–Barr virus-encoded nuclear protein EBNA-3 interacts with the epsilon-subunit of the T-complex protein 1 chaperonin complex. J. Hum. Virol., 2, 33–37.Google ScholarPubMed
Kashuba, E., Kashuba, V., Pokrovskaja, K., Klein, G., and Szekely, L. (2000). Epstein–Barr virus encoded nuclear protein EBNA-3 binds XAP-2, a protein associated with Hepatitis B virus X antigen. Oncogene, 19, 1801–1806.CrossRefGoogle ScholarPubMed
Kashuba, E., Kashuba, V., Sandalova, T., Klein, G., and Szekely, L. (2002). Epstein–Barr virus encoded nuclear protein EBNA-3 binds a novel human uridine kinase/uracil phosphoribosyltransferase. BMC Cell Biol., 3, 23.CrossRefGoogle ScholarPubMed
Kashuba, E., Mattsson, K., Pokrovskaja, K.et al. (2003). EBV-encoded EBNA-5 associates with P14ARF in extranucleolar inclusions and prolongs the survival of P14ARF-expressing cells. Int. J. Cancer, 105, 644–653.CrossRefGoogle ScholarPubMed
Kawanishi, M. (2000). The Epstein–Barr virus latent membrane protein 1 (LMP1) enhances TNF alpha-induced apoptosis of intestine 407 epithelial cells: the role of LMP1 C-terminal activation regions 1 and 2. Virology, 270, 258–266.CrossRefGoogle ScholarPubMed
Kaye, K. M., Izumi, K. M., Li, H.et al. (1999). An Epstein–Barr virus that expresses only the first 231 LMP1 amino acids efficiently initiates primary B-lymphocyte growth transformation. J. Virol., 73, 10525–10530.Google ScholarPubMed
Kempkes, B., Pawlita, M., Zimber-Strobl, U., Eissner, G., Laux, G., and Bornkamm, G. W. (1995). Epstein–Barr virus nuclear antigen 2-estrogen receptor fusion protein transactivate viral and cellular genes and interact with RBP-J kappa a conditional fashion. Virology, 214, 675–679.CrossRefGoogle ScholarPubMed
Kieser, A., Kilger, E., Gires, O., Ueffing, M., Kolch, W., and Hammerschmidt, W. (1997). Epstein–Barr virus latent membrane protein-1 triggers AP-1 activity via the c-Jun N-terminal kinase cascade. EMBO J., 16, 6478–6485.CrossRefGoogle ScholarPubMed
Kilger, E., Kieser, A., Baumann, M., and Hammerschmidt, W. (1998). Epstein–Barr virus-mediated B-cell proliferation is dependent upon latent membrane protein 1, which simulates an activated CD40 receptor. EMBO J., 17, 1700–1709.CrossRefGoogle ScholarPubMed
Kiss, C., Nishikawa, J., Takada, K., Trivedi, P., Klein, G., and Szekely, L. (2003). T cell leukemia 1 oncogene expression depends on the presence of Epstein–Barr virus in the virus-carrying Burkitt lymphoma lines. Proc. Natl Acad. Sci. USA, 100, 4813–4818.CrossRefGoogle ScholarPubMed
Klein, G., Pearson, G., Rabson, A.et al. (1973). Antibody reactions to herpesvirus Saimiri (HVS)-induced early and late antigens (EA and LA) in HVS-infected squirrel, marmoset and owl monkeys. Int. J. Cancer, 12, 270–289.CrossRefGoogle ScholarPubMed
Komano, J., Sugiura, M., and Takada, K. (1998). Epstein–Barr virus contributes to the malignant phenotype and to apoptosis resistance in Burkitt's lymphoma cell line AKATA. J. Virol., 72, 9150–9156.Google ScholarPubMed
Krauer, K. G., Burgess, A., Buck, M., Flanagan, J., Sculley, T. B., and Gabrielli, B. (2004). The EBNA-3 gene family proteins disrupt the G2/M checkpoint. Oncogene, 23, 1342–1353.CrossRefGoogle ScholarPubMed
Kuppers, R., Schwering, I., Brauninger, A., Rajewsky, K., and Hansmann, M. L. (2002). Biology of Hodgkin's lymphoma. Ann. Oncol., 13 Suppl 1:11–18.CrossRefGoogle ScholarPubMed
Lam, N., and Sugden, B. (2003). LMP1, a viral relative of the TNF receptor family, signals principally from intracellular compartments. EMBO J., 22, 3027–3038.CrossRefGoogle ScholarPubMed
Langerak, A. W., Moreau, E., Gastel-Mol, E. I., Burg, M., and Dongen, J. J. (2002) Detection of clonal EBV episomes in lymphoproliferations as a diagnostic tool. Leukemia, 16, 1572–1573.CrossRefGoogle ScholarPubMed
Laux, G., Perricaudet, M., and Farrell, P. J. (1988). A spliced Epstein–Barr virus gene expressed in immortalized lymphocytes is created by circularization of the linear viral genome. EMBO J., 7, 769–774.Google ScholarPubMed
Lee, B. S., Alvarez, X., Ishido, S., Lackner, A. A., and Jung, J. U. (2000). Inhibition of intracellular transport of B cell antigen receptor complexes by Kaposi's sarcoma-associated herpesvirus K1. J. Exp. Med., 192, 11–21.CrossRefGoogle ScholarPubMed
Lennette, E. T., Winberg, G., Yadav, M., Enblad, G., and Klein, G. (1995). Antibodies to LMP2A/2B in EBV-carrying malignancies. Eur. J. Cancer, 31A, 1875–1878.CrossRefGoogle ScholarPubMed
Levine, P. H., Pallesen, G., Ebbesen, P., Harris, N., Evans, A. S., and Mueller, N. (1994). Evaluation of Epstein–Barr virus antibody patterns and detection of viral markers in the biopsies of patients with Hodgkin's disease. Int. J. Cancer, 5948–5950.Google ScholarPubMed
Levitskaya, J., Coram, M., Levitsky, V.et al. (1995). Inhibition of antigen processing by the internal repeat region of the Epstein–Barr virus nuclear antigen-1. Nature, 375, 685–688.CrossRefGoogle ScholarPubMed
Lin, J., Johannsen, E., Robertson, E., and Kieff, E. (2002). Epstein–Barr virus nuclear antigen 3C putative repression domain mediates coactivation of the LMP1 promoter with EBNA-2. J. Virol., 76, 232–242.CrossRefGoogle ScholarPubMed
Lindahl, T., Klein, G., Reedman, B. M., Johansson, B., and Singh, S. (1974). Relationship between Epstein–Barr virus (EBV) DNA and the EBV-determined nuclear antigen (EBNA) in Burkitt lymphoma biopsies and other lymphoproliferative malignancies. Int. J. Cancer, 13, 764–772.CrossRefGoogle ScholarPubMed
Lindström, M. and Wiman, K. G. (2002). Role of genetic and epigenetic changes in Burkitt lymphoma. Semin. Cancer Biol., 12, 381–387.CrossRefGoogle ScholarPubMed
Lo, K. W. and Huang, D. P. (2002). Genetic and epigenetic changes in nasopharyngeal carcinoma. Semin. Cancer Biol., 12, 451–462.CrossRefGoogle ScholarPubMed
Longnecker, R. and Kieff, E. (1990). A second Epstein–Barr virus membrane protein (LMP2) is expressed in latent infection and colocalizes with LMP1. J. Virol., 64, 2319–2326.Google ScholarPubMed
Lynch, D. T., Zimmerman, J. S., and Rowe, D. T. (2002). Epstein–Barr virus latent membrane protein 2B (LMP2B) co-localizes with LMP2A in perinuclear regions in transiently transfected cells. J. Gen. Virol., 83, 1025–1035.CrossRefGoogle ScholarPubMed
Magrath, I. (1990). The pathogenesis of Burkitt's lymphoma, Adv. Cancer Res., 55, 133–269.CrossRefGoogle ScholarPubMed
Matskova, L., Ernberg, I., Pawson, T., and Winberg, G. (2001). C-terminal domain of the Epstein–Barr virus LMP2a protein contains a clustering signal. J. Virol., 75, 10941–10949.CrossRefGoogle ScholarPubMed
Mehl, A. M., Floettmann, J. E., Jones, M., Brennan, P., and Rowe, M. (2001). Characterization of intercellular adhesion molecule-1 regulation by Epstein–Barr virus-encoded latent membrane protein-1 identifies pathways that cooperate with nuclear factor kappa B to activate transcription. J. Biol. Chem., 276, 984–992.CrossRefGoogle ScholarPubMed
Miller, C. L., Lee, J. H., Kieff, E., and Longnecker, R. (1994). An integral membrane protein (LMP2) blocks reactivation of Epstein–Barr virus from latency following surface immunoglobulin crosslinking. Proc. Natl Acad. Sci. USA, 91, 772–776.CrossRefGoogle ScholarPubMed
Miyashita, E. M., Yang, B., Babcock, G. J., and Thorley-Lawson, D. A. (1997). Identification of the site of Epstein–Barr virus persistence in vivo as a resting B cell. J. Virol., 71, 4882–4891.Google ScholarPubMed
Molin, D., Fischer, M., Xiang, Z.et al. (2001). Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease. Br. J. Haematol., 114, 616–623.CrossRefGoogle ScholarPubMed
Montalban, C., Abraira, V., Morente, M.et al. (2000). Epstein–Barr virus-latent membrane protein 1 expression has a favorable influence in the outcome of patients with Hodgkin's Disease treated with chemotherapy. Leuk. Lymphoma, 39, 563–572.CrossRefGoogle Scholar
Morente, M. M., Piris, M. A., Abraira, V.et al. (1997). Adverse clinical outcome in Hodgkin's disease is associated with loss of retinoblastoma protein expression, high Ki67 proliferation index, and absence of Epstein–Barr virus-latent membrane protein 1 expression. Blood, 90, 2429–2436.Google ScholarPubMed
Mosialos, G., Birkenbach, M., Yalamanchili, R., VanArsdale, T., Ware, C., and Kieff, E. (1995). The Epstein–Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell., 80, 389–399.CrossRefGoogle ScholarPubMed
Murray, P. G., Billingham, L. J., Hassan, H. T., and Young, L. S. (1999). Epstein–Barr virus infection on response to chemotherapy and survival in Hodgkin's disease. Blood, 94, 442–447.Google ScholarPubMed
Muschen, M., Re, D., Brauninger, A.et al. (2000). Somatic mutations of the CD95 gene in Hodgkin and Reed–Sternberg cells. Cancer Res., 60, 5640–5643.Google ScholarPubMed
Nicholas, J. (2003). Human herpesvirus-8-encoded signalling ligands and receptors. J. Biomed. Sci., 10, 475–489.CrossRefGoogle ScholarPubMed
Niedobitek, G., Deacon, E. M., and Young, L. S. (1989). Epstein–Barr virus gene expression in Hodgkin's disease. Blood, 78, 1628–1630.Google Scholar
Nishikawa, J., Kiss, C., Imai, S.et al. (2003). Upregulation or the truncated basic hair keratin 1(hHb1-ΔN) in carcinoma cells by Epstein–Barr virus (EBV). Internat. J. Cancer, 107, 597–602.Google Scholar
Ohno, S., Luka, J., Lindahl, T., and Klein, G. (1977). Identification of a purified complement-fixing antigen as the Epstein–Barr-virus determined nuclear antigen (EBNA) by its binding to metaphase chromosomes. Proc. Natl Acad. Sci. USA, 74, 1605–1609.CrossRefGoogle ScholarPubMed
Ohshima, K., Suzumiya, J., Tasiro, K.et al. (1996). Epstein–Barr virus infection and associated products (LMP, EBNA2, vIL-10) in nodal non-Hodgkin's lymphoma of human immunodeficiency virus-negative Japanese. Am. J. Hematol., 52(1), 21–28.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
Parker, G. A., Crook, T., Bain, M., Sara, E. A., Farrell, P. J., and Allday, M. J. (1996). Epstein–Barr virus nuclear antigen (EBNA)3C is an immortalizing oncoprotein with similar properties to adenovirus E1A and papillomavirus E7. Oncogene, 13, 2541–2549.Google ScholarPubMed
Parker, G. A., Touitou, R., and Allday, M. J. (2000). Epstein–Barr virus EBNA3C can disrupt multiple cell cycle checkpoints and induce nuclear division divorced from cytokinesis. Oncogene, 19, 700–709.CrossRefGoogle ScholarPubMed
Pathmanathan, R., Prasad, U., Sadler, R., Flynn, K., and Raab-Traub, N. (1995). Clonal proliferations of cells infected with Epstein–Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. N. Engl. J. Med., 333, 693–698.CrossRefGoogle ScholarPubMed
Polack, A., Hortnagel, K., Pajic, A.et al. (1996). c-myc activation renders proliferation of Epstein–Barr virus (EBV)-transformed cells independent of EBV nuclear antigen 2 and latent membrane protein 1. Proc. Natl Acad. Sci. USA, 93, 10411–10416.CrossRefGoogle ScholarPubMed
Polvino-Bodnar, M., Kiso, J., and Schaffer, P. A. (1988). Mutational analysis of Epstein–Barr virus nuclear antigen 1 (EBNA 1). Nucl. Acids Res., 16, 3415–3435.CrossRefGoogle Scholar
Pokrovskaja, K., Mattsson, K., Kashuba, E., Klein, G., and Szekely, L. (2001). Inhibitor induces nucleolar translocation of Epstein–Barr virus-encoded EBNA-5. J. Gen. Virol., 82, 345–358.CrossRefGoogle ScholarPubMed
Prevot, S., Hamilton-Dutoit, S., Audouin, J., Walter, P., Pallesen, G., and Diebold, J. (1992). Analysis of African Burkitt's and high-grade B cell non-Burkitt's lymphoma for Epstein–Barr virus genomes using in situ hybridization. Br. J. Haematol, 80, 27–32.CrossRefGoogle ScholarPubMed
Qu, L. and Rowe, D. T. (1992). Epstein–Barr virus latent gene expression in uncultured peripheral blood lymphocytes. J. Virol., 66, 3715–3724.Google ScholarPubMed
Radkov, S. A., Bain, M., Farrell, P. J., West, M., Rowe, M., and Allday, M. J. (1997). Epstein–Barr virus EBNA3C represses Cp, the major promoter for EBNA expression, but has no effect on the promoter of the cell gene CD21. J. Virol., 71, 8552–8562.Google ScholarPubMed
Radkov, S. A., Touitou, R., Brehm, A.et al. (1999). Epstein–Barr virus nuclear antigen 3C interacts with histone deacetylase to repress transcription. J. Virol., 73, 5688–5697.Google ScholarPubMed
Radkov, S., Kellam, P., and Boshoff, C. (2000). The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene Hras transforms primary rat cells. Nat. Med., 6, 1121–1127.CrossRefGoogle ScholarPubMed
Rawlins, D. R., Milman, G., Hayward, S. D., and Hayward, G. S. (1985). Sequence-specific DNA binding of the Epstein–Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell, 42, 859–868.CrossRefGoogle ScholarPubMed
Rea, D., Fourcade, C., Leblond, V.et al. (1994). Patterns of Epstein–Barr virus latent and replicative gene expression in Epstein–Barr virus B cell lymphoproliferative disorders after organ transplantation. Transplantation, 58, 317–324.CrossRefGoogle ScholarPubMed
Reedman, B. M. and Klein, G. (1973). Related Articles, Cellular localization of an Epstein–Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int. J. Cancer, 11, 499–520.CrossRefGoogle Scholar
Reisman, D. and Sugden, B. (1986). Trans-activation of an Epstein–Barr viral transcriptional enhancer by the Epstein–Barr viral nuclear antigen 1. Mol. Cell Biol., 6, 3838–3846.CrossRefGoogle ScholarPubMed
Rickinson, A. B., Young, L. S., and Rowe, M. (1987). Influence of the Epstein–Barr virus nuclear antigen EBNA 2 on the growth phenotype of virus-transformed B cells. J. Virol., 61, 1310–1317.Google ScholarPubMed
Rous, P. (1911). A sarcoma of fowl transmissible by an agent from the tumor cells. J. Exp. Med., 13, 397–411.CrossRefGoogle ScholarPubMed
Rowe, M., Young, L. S., Cadwallader, K., Petti, L., Kieff, E., and Rickinson, A. B. (1989). Distinction between Epstein–Barr virus type A (EBNA 2A) and type B (EBNA 2B) isolates extends to the EBNA 3 family of nuclear proteins. J. Virol., 63, 1031–1039.Google ScholarPubMed
Rowe, M., Khanna, R., Jacob, C. A.et al. (1995). Restoration of endogenous antigen processing in Burkitt's lymphoma cells by Epstein–Barr virus latent membrane protein-1: coordinate up-regulation of peptide transporters and HLA-class I antigen expression. Eur. J. Immunol., 25, 1374–1384.CrossRefGoogle ScholarPubMed
Scholle, F., Bendt, K. M., and Raab-Traub, N. (2000). Epstein–Barr virus LMP2A transforms epithelial cells, inhibits cell differentiation, and activatesAkt. J. Virol., 74, 10681–10689.CrossRefGoogle ScholarPubMed
Sample, J. and Kieff, E. (1990). Transcription of the Epstein–Barr virus genome during latency in growth-transformed lymphocytes. J. Virol., 64, 1667–1674.Google ScholarPubMed
Shimizu, N., Yamaki, M., Sakuma, S., Ono, Y., and Takada, K. (1988). Three Epstein–Barr virus (EBV)-determined nuclear antigens induced by the BamHI E region of EBV DNA. Int. J. Cancer, 41, 744–751.CrossRefGoogle Scholar
Shope, R. E. (1933). Infectious papillomatosis of rabbits; with a note on the histopathology. J. Exp. Med., 68, 607–624.CrossRefGoogle Scholar
Spieker, T., Kurth, J., Kuppers, R., Rajewsky, K., Brauninger, A., and Hansmann, M. L. (2000). Molecular single-cell analysis of the clonal relationship of small Epstein–Barr virus-infected cells and Epstein–Barr virus-harboring Hodgkin and Reed/Sternberg cells in Hodgkin disease. Blood., 96, 3133–3138.Google ScholarPubMed
Stewart, S-E., Eddy, B-E., and Borgear, N. (1958). Neoplasms in mice inoculated with a tumor agent carried in tissue culture. J. Natl Cancer Inst., 20, 1223–1243.CrossRefGoogle ScholarPubMed
Sugden, B. and Warren, N. (1989). A promoter of Epstein–Barr virus that can function during latent infection can be transactivated by EBNA-1, a viral protein required for viral DNA replication during latent infection. J. Virol., 63, 2644–2649.Google ScholarPubMed
Swart, R., Ruf, I. K., Sample, J., and Longnecker, R. (2000). Latent membrane protein 2A-mediated effects on the phosphatidylinositol 3-kinase/Akt pathway. J. Virol., 74, 10838–10845.CrossRefGoogle ScholarPubMed
Takada, K. (2001). Role of Epstein–Barr virus in Burkitt's lymphoma. Curr. Top. Microbiol. Immunol., 258, 141–161.Google ScholarPubMed
Tamura, K., Taniguchi, Y., Minoguchi, S.et al. (1995). Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-Jk. Curr. Biol., 5, 1416–1423.CrossRefGoogle Scholar
Tan, L. C., Gudgeon, N., Annels, N.et al. (1999). Re-evaluation of the frequency of CD8+ T cells specific for EBV in healthy virus carriers. J. Immunol., 162, 1827–1835.Google ScholarPubMed
Tepper, C. and Seldin, M. (1999). Modulation of Casoase-8 and FLICE-inhibitory proytein expression as a potential mechanism of Epstein–Barr virus tumorigeneis in Burkitt's lymphoma. Blood, 94, 1727–1737.Google Scholar
Tierney, R. J., Steven, N., Young, L. S., and Rickinson, A. B. (1994). Epstein–Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J. Virol., 68, 7374–7385.Google ScholarPubMed
Touitou, R., Hickabottom, M., Parker, G., Crook, T., and Allday, M. J. (2001). Physical and functional interactions between the corepressor CtBP and the Epstein–Barr virus nuclear antigen EBNA3C. J. Virol., 75, 7749–7755.CrossRefGoogle ScholarPubMed
Verschueren, E. W., Klefstrom, J., Evan, G. I., and Jones, N. (2002). The oncogeneic potential of Kaposi's sarcoma-associated herpesvirus cyclin is exposed by p53 loss in vitro and in vivo. Cancer Cell, 2, 229–241.CrossRefGoogle Scholar
Wang, F., Gregory, C. D., Rowe, M.et al. (1987a). Epstein–Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23. Proc. Natl Acad. Sci. USA, 84, 3452–3456.CrossRefGoogle Scholar
Wang, F., Petti, L., Braun, D., Seung, S., and Kieff, E. (1987b). Free in PMC A bicistronic Epstein–Barr virus mRNA encodes two nuclear proteins in latently infected, growth-transformed lymphocytes. J. Virol., 61, 945–954.Google Scholar
Wang, F., Gregory, C., Sample, C.et al. (1990). Epstein–Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J. Virol., 64, 2309–2318.Google Scholar
Webster-Cyriaque, J. and Raab-Traub, N. (1998). Transcription of Epstein–Barr virus latent cycle genes in oral hairy leukoplakia. Virology, 248, 53–65.CrossRefGoogle ScholarPubMed
Weng, A. P., Shahsafaei, A., and Dorfman, D. M. (2003). CXCR4/CD184 immunoreactivity in T-cell non-Hodgkin lymphomas with an overall Th1-Th2+ immunophenotype. Am. J. Clin. Pathol., 119, 424–430.CrossRefGoogle ScholarPubMed
West, M. J., Webb, H. M., Sinclair, A. J., and , Woolfson DN. (2004). Biophysical and mutational analysis of the putative bZIP domain of Epstein–Barr virus EBNA 3C. J. Virol., 78, 9431–9445.CrossRefGoogle ScholarPubMed
Winberg, G., Matskova, L., Chen, F.et al. (2000). Latent membrane protein 2A of Epstein–Barr virus binds WW domain E3 protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases. Mol. Cell, 20, 8526–8535.CrossRefGoogle ScholarPubMed
Zhang, X., Hu, L., Fadeel, B., and Ernberg, I. T. (2002). Apoptosis modulation of Epstein–Barr virus-encoded latent membrane protein 1 in the epithelial cell line HeLa is stimulus-dependent. Virology, 304, 330–341.CrossRefGoogle ScholarPubMed
Zhao, B., Dalbies-Tran, R., Jiang, H.et al. (2003). Transcriptional regulatory properties of Epstein–Barr virus nuclear antigen 3C are conserved in simian lymphocryptoviruses. J. Virol., 77, 5639–5648.CrossRefGoogle ScholarPubMed
Zimber, U., Adldinger, H. K., Lenoir, G. M.et al. (1986). Geographical prevalence of two types of Epstein–Barr virus. Virology, 154, 56–66.CrossRefGoogle ScholarPubMed
Zimber-Strobl, U., Kempkes, B., Marschall, G.et al. (1996). Epstein–Barr virus latent membrane protein (LMP1) is not sufficient to maintain proliferation of B cells but both it and activated CD40 can prolong their survival. EMBO J., 15, 7070–7078.Google Scholar
Zhou, X. G., Hamilton-Dutoit, S. J., Yan, Q. H., and Pallesen, G. (1994). High frequency of Epstein–Barr virus in Chinese peripheral T-cell lymphoma. Histopathology, 24, 115–122.CrossRefGoogle ScholarPubMed

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