Advertisement

Targeting Viral Antigens for the Treatment of Malignancies

  • Gretchen L. Eiben
  • Diane M. Da Silva
  • Steven C. Fausch
  • Amanda M. Krier
  • I. Caroline Le Poole
  • Megan E. Papineau
  • Michael I. Nishimura
  • W. Martin Kast
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Viruses implicated in the development of human cancer include hepatitis B (HBV) and hepatitis C (HCV) viruses, human papilloma virus (HPV), Epstein-Barr virus (EBV), human T-cell lymphoma virus, and human herpes virus 8. Together they contribute significantly to the total incidence of cancer worldwide. Current work in each of these virus systems seeks to understand the mechanisms of viral action and identify strategies of immune intervention to combat viral infection and subsequent transformation. It is thought that oncogenic proliferation may be instigated by the presence and expression of viral oncogenes, which may be integrated into the host genome. Critical viral genes may also interfere with host genes, resulting in the activation of cellular proto-oncogenes and/or the inactivation of anti-oncogenes and their products. Targeting such viral proteins through various vaccination strategies offers both therapeutic and prophylactic strategies against viral induced malignancies.

Keywords

Human Leukocyte Antigen Human Papilloma Virus Latent Membrane Protein Venezuelan Equine Encephalitis Virus Specific CTLs 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Rous P. Landmark article. JAMA 1911; 56:198.Google Scholar
  2. 1a.
    Rous P. Transmission of a malignant new growth by means of a cell-free filtrate. By Peyton Rous. JAMA 1983; 250:1445–1449.PubMedCrossRefGoogle Scholar
  3. 2.
    Shope RE. Infectious papillomatosis of rabbits; with a note on histopathology. J Exp Med 1933; 68: 607–624.CrossRefGoogle Scholar
  4. 3.
    de The G, Geser A, Day NE, Tukei PM, Williams EH, Beni DP, Smith PG, Dean AG, Bronkamm GW, Feorino P, Henle W. Epidemiological evidence for causal relationship between Epstein-Barr virus and Burkitt’ s lymphoma from Ugandan prospective study. Nature 1978; 274:756–761.CrossRefGoogle Scholar
  5. 4.
    Epstein MA. Reflections on Epstein-Barr virus: some recently resolved old uncertainties. J Infect 2001; 43:111–115.PubMedCrossRefGoogle Scholar
  6. 5.
    Klein G. Perspectives in studies of human tumor viruses. Front Biosci 2002; 7:d268–d274.PubMedCrossRefGoogle Scholar
  7. 6.
    Greenberg PD. Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells. Adv Immunol 1991; 49:281–355.PubMedCrossRefGoogle Scholar
  8. 7.
    Klein G. Epstein-Barr virus strategy in normal and neoplastic B cells. Cell 1994; 77:791–793.PubMedCrossRefGoogle Scholar
  9. 8.
    Cohen JI. Epstein-Barr virus infection. N Engl J Med 2000; 343:481–492.PubMedCrossRefGoogle Scholar
  10. 9.
    Weiss LM, Movahed LA, Warnke RA, Sklar J. Detection of Epstein-Barr viral genomes in ReedSternberg cells of Hodgkin’s disease. N Engl J Med 1989; 320:502–506.PubMedCrossRefGoogle Scholar
  11. 10.
    Khanna R, Moss DJ, Burrows SR. Vaccine strategies against Epstein-Barr virus-associated diseases: lessons from studies on cytotoxic T-cell-mediated immune regulation. Immunol Rev 1999; 170:49–64.PubMedCrossRefGoogle Scholar
  12. 11.
    Hopwood P, Crawford DH. The role of EBV in post-transplant malignancies: a review. J Clin Pathol 2000; 53:248–254.PubMedCrossRefGoogle Scholar
  13. 12.
    Khanna R, Burrows SR, Kurilla MG, Jacob CA, Misko IS, Sculley TB, Kieff E, Moss DJ. Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development. J Exp Med 1992; 176:169–176.PubMedCrossRefGoogle Scholar
  14. 13.
    Blake N, Lee S, Redchenko I, Thomas W, Steven N, Leese A, Steigerwald-Mullen P, Kurilla MG, Frappier L, Rickinson A. Human CD8+ T cell responses to EBV EBNAl: HLA class I presentation of the (Gly-Ala)-containing protein requires exogenous processing. Immunity 1997; 7:791–802.PubMedCrossRefGoogle Scholar
  15. 14.
    Khanna R, Burrows SR, Argaet V, Moss DJ. Endoplasmic reticulum signal sequence facilitated transport of peptide epitopes restores immunogenicity of an antigen processing defective tumour cell line. Int Immunol 1994; 6:639–645.PubMedCrossRefGoogle Scholar
  16. 15.
    Khanna R, Burrows SR, Nicholls J, Poulsen LM. Identification of cytotoxic T cell epitopes within Epstein-Barr virus (EBV) oncogene latent membrane protein 1 (LMP1): evidence for HLA A2 supertyperestricted immune recognition of EBV-infected cells by LMPl-specific cytotoxic T lymphocytes. Eur J Immunol 1998; 28:451–458.PubMedCrossRefGoogle Scholar
  17. 16.
    Lee SP, Tierney RJ, Thomas WA, Brooks JM, Rickinson AB. Conserved CTL epitopes within EBV latent membrane protein 2: a potential target for CTL-based tumor therapy. J Immunol 1997; 158:3325–3334.PubMedGoogle Scholar
  18. 17.
    Frisan T, Donati D, Cervenak L, Wilson J, Masucci MG, Bejarano MT. CD40 cross-linking enhances the immunogenicity of Burkitt’ s-lymphoma cell lines. Int J Cancer 1999; 83:772–779.PubMedCrossRefGoogle Scholar
  19. 18.
    Munz C, Bickham KL, Subklewe M, Tsang ML, Chahroudi A, Kurilla MG, Zhang D, O’Donnell M, Steinman RM. Human CD4(+) T lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNAl. J Exp Med 2000; 191:1649–1660.PubMedCrossRefGoogle Scholar
  20. 19.
    Roskrow MA, Suzuki N, Gan Y, Sixbey JW, Ng CY, Kimbrough S, Hudson M, Brenner MK, Heslop HE, Rooney CM. Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for the treatment of patients with EBV-positive relapsed Hodgkin’s disease. Blood 1998; 91:2925–2934.PubMedGoogle Scholar
  21. 20.
    Rooney CM, Roskrow MA, Smith CA, Brenner MK, Heslop HE. Immunotherapy for Epstein-Barr virus-associated cancers. J Natl Cancer Inst Monogr 1998; 23:89–93.PubMedCrossRefGoogle Scholar
  22. 21.
    Starzl TE, Nalesnik MA, Porter KA, Ho M, Iwatsuki S, Griffith BP, Rosenthal JT, Hakala TR, Shaw BW Jr, Hardesty RL, et al. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet 1984; 1:583–587.PubMedCrossRefGoogle Scholar
  23. 22.
    Rooney CM, Smith CA, Ng CY, Loftin S, Li C, Krance RA, Brenner MK, Heslop HE. Use of genemodified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet 1995; 345:9–13.PubMedCrossRefGoogle Scholar
  24. 23.
    Clay TM, Custer MC, Sachs J, Hwu P, Rosenberg SA, Nishimura MI. Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity. J Immunol 1999; 163:507–513.PubMedGoogle Scholar
  25. 24.
    Wogan GN. Impacts of chemicals on liver cancer risk. Semin Cancer Biol 2000; 10:201–210.PubMedCrossRefGoogle Scholar
  26. 25.
    Prince AM. Perspectives on prophylactic and therapeutic immunization against hepatitis B and C viruses. Transfus Clin Biol 2001; 8:467–470.PubMedCrossRefGoogle Scholar
  27. 26.
    Yotsuyanagi H, Shintani Y, Moriya K, Fujie H, Tsutsumi T, Kato T, Nishioka K, Takayama T, Makuuchi M, lino S, Kimura S, Koike K. Virologic analysis of non-B, non-C hepatocellular carcinoma in Japan: frequent involvement of hepatitis B virus. J Infect Dis 2000; 181:1920–1928.PubMedCrossRefGoogle Scholar
  28. 27.
    Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nakano Y, Furuta S, Akahane Y, Nishioka K, Purcell RH, et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology 1990; 12:671–675.PubMedCrossRefGoogle Scholar
  29. 28.
    Moriya K, Yotsuyanagi H, Shintani Y, Fujie H, Ishibashi K, Matsuura Y, Miyamura T, Koike K. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J Gen Virol 1997; 78:1527–1531.PubMedGoogle Scholar
  30. 29.
    Chisari FV. Hepatitis B virus transgenic mice: insights into the virus and the disease. Hepatology 1995; 22:1316–1325.PubMedGoogle Scholar
  31. 30.
    Hilleman MR. Overview of the pathogenesis, prophylaxis and therapeusis of viral hepatitis B, with focus on reduction to practical applications. Vaccine 2001; 19:1837–1848.PubMedCrossRefGoogle Scholar
  32. 31.
    Sherlock S, Fox RA, Niazi SP, Scheuer PJ. Chronic liver disease and primary liver-cell cancer with hepatitis-associated (Australia) antigen in serum. Lancet 1970; 1:1243–1247.PubMedCrossRefGoogle Scholar
  33. 32.
    Koike K, Moriya K, Yotsuyanagi H, Iino S, Kurokawa K. Induction of cell cycle progression by hepatitis B virus HBx gene expression in quiescent mouse fibroblasts. J Clin Invest 1994; 94:44–49.PubMedCrossRefGoogle Scholar
  34. 33.
    Benn J, Schneider RJ. Hepatitis B virus HBx protein deregulates cell cycle checkpoint controls. Proc Natl Acad Sci USA 1995; 92:11215–11219.PubMedCrossRefGoogle Scholar
  35. 34.
    Kim CM, Koike K, Saito I, Miyamura T, Jay G. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 1991; 351:317–320.PubMedCrossRefGoogle Scholar
  36. 35.
    Yu DY, Moon HB, Son JK, Jeong S, Yu SL, Yoon H, Han YM, Lee CS, Park JS, Lee CH, Hyun BH, Murakami S, Lee KK. Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein. J Hepatol 1999; 31:123–132.PubMedCrossRefGoogle Scholar
  37. 36.
    Lauer U, Weiss L, Lipp M, Hofschneider PH, Kekule AS. The hepatitis B virus preS2/St transactivator utilizes AP-1 and other transcription factors for transactivation. Hepatology 1994; 19:23–31.PubMedGoogle Scholar
  38. 37.
    Huang K, Lin S. Nationwide vaccination: a success story in Taiwan. Vaccine 2000; 18(Suppl 1):535–538.Google Scholar
  39. 38.
    Chang MH, Shau WY, Chen CJ, Wu TC, Kong MS, Liang DC, Hsu HM, Chen HL, Hsu HY, Chen DS. Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls. JAMA 2000; 284:3040–3042.PubMedCrossRefGoogle Scholar
  40. 39.
    Tang L, Tanaka Y, Enomoto N, Marumo F, Sato C. Detection of hepatitis C virus RNA in hepatocellular carcinoma by in situ hybridization. Cancer 1995; 76:2211–2216.PubMedCrossRefGoogle Scholar
  41. 40.
    Shih CM, Lo SJ, Miyamura T, Chen SY, Lee YH. Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH-7 cells. J Virol 1993; 67:5823–5832.PubMedGoogle Scholar
  42. 41.
    Ray RB, Steele R, Meyer K, Ray R. Transcriptional repression of p53 promoter by hepatitis C virus core protein. J Biol Chem 1997; 272:10983–10986.PubMedCrossRefGoogle Scholar
  43. 42.
    He XS, Rivkina M, Robinson WS. Construction of adenoviral and retroviral vectors coexpressing the genes encoding the hepatitis B surface antigen and B7–1 protein. Gene 1996: 175:121–125.PubMedCrossRefGoogle Scholar
  44. 43.
    Davis HL, Schirmbeck R, Reimann J, Whalen RG. DNA-mediated immunization in mice induces a potent MHC class I-restricted cytotoxic T lymphocyte response to the hepatitis B envelope protein. Hum Gene Ther 1995; 6:1447–1456.PubMedCrossRefGoogle Scholar
  45. 44.
    Pisani P, Bray F, Parkin DM. Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. Int J Cancer 2002; 97:72–81.PubMedCrossRefGoogle Scholar
  46. 45.
    Munoz N. Human papillomavirus and cancer: The epidemiological evidence. J Clin Virol 2000;19: 1–5.CrossRefGoogle Scholar
  47. 46.
    Seedorf K, Oltersdorf T, Krammer G, Rowekamp W. Identification of early proteins of the human papilloma viruses type 16 (HPV 16) and type 18 (HPV 18) in cervical carcinoma cells. EMBO J 1987; 6:139–144.PubMedGoogle Scholar
  48. 47.
    Von Knebel Doeberitz M, Bauknecht T, Bartsch D, zur Hausen H. Influence of chromosomal integration on glucocorticoid regulated transcription of growth-stimulating papillomavirus E6 E7 genes in cervical carcinoma cells. Proc Natl Acad Sci USA 1991: 88:1411–1415.CrossRefGoogle Scholar
  49. 48.
    Werness BA, Levine Ai, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 1990; 248:76–79.PubMedCrossRefGoogle Scholar
  50. 49.
    Dyson N, Howley PM, Munger K Harlow E. The human papillomavirus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 1989; 243:934–940.PubMedCrossRefGoogle Scholar
  51. 50.
    Crish JF, Bone F, Balasubramanian S, Zaim TM, Wagner T, Yun J, Rorke EA, Eckert RL. Suprabasal expression of the human papillomavirus type 16 oncoproteins in mouse epidermis alters expression of cell cycle regulatory proteins. Carcinogenesis 2000; 21:1031–1037.PubMedCrossRefGoogle Scholar
  52. 51.
    Durst M, Glitz D, Schneider A, zur Hausen H. Human papillomavirus type 16 (HPV 16) gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridization. Virology 1992: 1 89:132–140.CrossRefGoogle Scholar
  53. 52.
    Sun W, Kuhn L, Ellerbrock T, Chiasson M, Bush T, Wright T. Human papillomavirus infection in women infected with the human immunodeficiency virus. N Engl J Med 1997; 337:1343–1349.PubMedCrossRefGoogle Scholar
  54. 53.
    Frisch M, Biggar Ri, Goedert JJ. Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst 2000; 92:1500–1510.PubMedCrossRefGoogle Scholar
  55. 54.
    Lin KY, Guarnieri FG, Staveley-O’ Carroll KF, Levitsky HI, August JT, Pardoll DM, Wu TC. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 1996; 56:21–26.PubMedGoogle Scholar
  56. 55.
    Velders MP, McElhiney S, Cassetti MC, Eiben GL, Higgins T, Kovacs GR, Elmishad AG, Kast WM, Smith LR. Eradication of established tumors by vaccination with Venezuelan equine encephalitis virus replicon particles delivering human papillomavirus 16 E7 RNA. Cancer Res 2001; 61:7861–7867.PubMedGoogle Scholar
  57. 56.
    Feltkamp MCW, Smits HL, Vierboom MPM, Minnaar RP, de Jongh BM, Drijfhout JW, ter Schegget J, Melief CJM, Kast WM. Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus type 16-transformed cells. Eur J Immunol 1993; 23:2242–2249.PubMedCrossRefGoogle Scholar
  58. 57.
    Fernando GJ, Murray B, Zhou J, Frazer IH. Expression, purification and immunological characterization of the transforming protein E7, from cervical cancer-associated human papillomavirus type 16. Clin Exp Immunol 1999; 115:397–403.PubMedCrossRefGoogle Scholar
  59. 58.
    Debruijn MLH, Schuurhuis DH, Vierboom MPM, Vermeulen H, Decock KAJ, Ooms ME, Ressing ME, Toebes M, Franken KLMC, Drijfhout JW, Ottenhoff THM, Offringa R, Melief CJM. Immunization with human papillomavirus type 16 (HPV16) oncoprotein-loaded dendritic cells as well as protein in adjuvant induces MHC class I-restricted protection to HPV16-induced tumor cells. Cancer Res 1998; 58:724–731.Google Scholar
  60. 59.
    Shi W, Bu P, Liu J, Polack A, Fisher S, Qiao L. Human papillomavirus type 16 E7 DNA vaccine: mutation in the open reading frame of E7 enhances specific cytotoxic T-lymphocyte induction and antitumor activity. J Virol 1999; 73:7877–7881.PubMedGoogle Scholar
  61. 60.
    Greenstone HL, Nieland JD, de Visser KE, De Bruijn ML, Kimbauer R, Roden RBS, Lowy DR, Kast WM, Schiller JT. Chimeric papillomavirus virus-like particles elicit antitumor immunity against the E7 oncoprotein in an HPV16 tumor model. Proc Nat Acad Sci USA 1998; 95:1800–1805.PubMedCrossRefGoogle Scholar
  62. 61.
    Peng S, Frazer IH, Fernando GJ, Zhou J. Papillomavirus virus-like particles can deliver defined CTL epitopes to the MHC class I pathway. Virology 1998; 240:147–157.PubMedCrossRefGoogle Scholar
  63. 62.
    Schafer K, Muller M, Faath S, Henn A, Osen W, Zentgraff H, Benner A, Gissmann L, Jochmus I. Immune response to human papillomavirus 16 LlE7 chimeric virus-like particles: induction of cytotoxic T cells and specific tumor protectin. Int J Cancer 1999; 81:881–888.PubMedCrossRefGoogle Scholar
  64. 63.
    Ji H, Wang TL, Chen CH, Pai SI, Hung CF, Lin KY, Kurman RJ, Pardoll DM, Wu TC. Targeting human papillomavirus type 16 E7 to the endosomal/lysosomal compartment enhances the antitumor immunity of DNA vaccines against murine human papillomavirus type 16 E7-expressing tumors. Hum Gene Ther 1999; 10:2727–2740.PubMedCrossRefGoogle Scholar
  65. 64.
    Velders MP, Weijzen S, Eiben GL, Elmishad AG, Kloetzel PM, Higgins T, Ciccarelli RB, Evans M, Man S, Smith L, Kast WM. Defined flanking spacers and enhanced proteolysis is essential for eradication of established tumors by an epitope string DNA vaccine. J Immunol 2001; 166:5366–5373.PubMedGoogle Scholar
  66. 65.
    Toes REM, Offringa R, Blom RJJ, Melief CJM, Kast WM. Peptide vaccination can lead to enhance tumor growth through specific T-cell tolerance induction. Proc Natl Acad Sci USA 1996; 93:7855–7860.PubMedCrossRefGoogle Scholar
  67. 66.
    Da Silva DM, Eiben GL, Fausch SC, Wakabayashi MT, Rudolf MP, Velders MP, Kast, WM. Cervical cancer vaccines: emerging concepts and developments. J Cell Physiol 2001; 186:169–182.PubMedCrossRefGoogle Scholar
  68. 67.
    MacDonald GH, Johnston RE. Role of dendritic cell targeting in Venezuelan equine encephalitis virus pathogenesis. J Virol 2000; 74:914–922.PubMedCrossRefGoogle Scholar
  69. 68.
    Da Silva DM, Pastrana DV, Schiller JT, Kast WM. Effect of preexisting neutralizing antibodies on the anti-tumor immune response induced by chimeric human papillomavirus virus-like particle vaccines. Virology 2001; 290:350–360.PubMedCrossRefGoogle Scholar
  70. 69.
    Ressing ME, van Driel WJ, Brandt RMP, Kenter GG, de Jong JH, Bauknecht T, Fleuren GJ, Hoogerhout P, Offringa R, Sette A, Celis E, Grey H, Trimbos BJ, Kast WM, Melief CJM. Detection of T helper responses, but not of human papillomavirus-specific cytotoxic T lymphocyte responses, after peptide vaccination of patients with cervical carcinoma. J Immunother 2000; 23:255–266.PubMedCrossRefGoogle Scholar
  71. 70.
    van Driel WJ, Ressing ME, Kenter GG, Brandt RM, Krul EJ, van Rossum AB, Schuuring E, Offringa R, Bauknecht T, Tamm-Hermelink A, van Dam PA, Fleuren GJ, Kast WM, Melief CJ, Trimbos JB. Vaccination with HPV16 peptides of patients with advanced cervical carcinoma: clinical evaluation of a nhase I-II trial Fur J Cancer 1999: 35:946–952.Google Scholar
  72. 71.
    Muderspach L, Wilczyneki S, Roman L, Bade L, Felix J, Small LA, Kast WM, Fascia G, Marty V, Weber J. A phase I trial of a HPV peptide vaccine for women with high grade cervical and vulvar intraepithelial neoplasia who are HPV 16 positive. Clin Cancer Res 2000; 6:3406–3416.PubMedGoogle Scholar
  73. 72.
    Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’ s sarcoma. Science 1994; 266:1865–1869.PubMedCrossRefGoogle Scholar
  74. 73.
    Friedman-Kien AE. Disseminated Kaposi’ s sarcoma syndrome in young homosexual men. J Am Acad Dermatol 1981; 5:468–471.PubMedCrossRefGoogle Scholar
  75. 74.
    Ablashi DV, Chatlynne LG, Whitman JJ Jr, Cesarman E. Spectrum of Kaposi’ s sarcoma-associated herpesvirus, or human herpesvirus 8, diseases. Clin Microbiol Rev 2002; 15:439–464.PubMedCrossRefGoogle Scholar
  76. 75.
    Sturzl M, Hohenadl C, Zietz C, Castanos-Velez E, Wunderlich A, Ascherl G, Biberfeld P, Monini P, Browning PJ, Ensoli B. Expression of K13/v-FLIP gene of human herpesvirus 8 and apoptosis in Kaposi’ s sarcoma spindle cells. J Natl Cancer Inst 1999; 91:1725–1733.PubMedCrossRefGoogle Scholar
  77. 76.
    Sturzl M, Wunderlich A, Ascherl G, Hohenadl C, Monini P, Zietz C, Browning PJ, Neipel F, Biberfeld P, Ensoli B. Human herpesvirus-8 (HHV-8) gene expression in Kaposi’ s sarcoma (KS) primary lesions: an in situ hybridization study. Leukemia 1999; 13 (Suppl 1): 5110–5112.Google Scholar
  78. 77.
    Staskus KA, Zhong W, Gebhard K, Herndier B, Wang H, Renne R, Beneke J, Pudney J, Anderson DJ, Ganem D, Haase AT. Kaposi’s sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol 1997; 71:715–719.PubMedGoogle Scholar
  79. 78.
    Radkov SA, Kellam P, Boshoff C. 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 2000; 6:1121–1127.PubMedCrossRefGoogle Scholar
  80. 79.
    Thome M., Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer JL, Schroter M, Scaffidi C, Krammer PH, Peter ME, Tschopp J. Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 1997; 386:517–521.PubMedCrossRefGoogle Scholar
  81. 80.
    Chang HC, Samaniego F, Nair BC, Buonaguro L, Ensoli B. HIV-1 Tat protein exits from cells via a leaderless secretory pathway and binds to extracellular matrix-associated heparan sulfate proteoglycans through its basic region. AIDS 1997; 11:1421–1431.PubMedCrossRefGoogle Scholar
  82. 81.
    Yamaguchi K, Takatsuki K. Adult T cell leukaemia-lymphoma. Baillieres Clin Haematol 1993; 6: 899–915.PubMedCrossRefGoogle Scholar
  83. 82.
    Yamaguchi K, Yoshioka R, Kiyokawa T, Seiki M, Yoshida M, Takatsuki K. Lymphoma type adult Tcell leukemia—a clinicopathologic study of HTLV related T-cell type malignant lymphoma. Hematol Oncol 1986; 4:59–65.PubMedCrossRefGoogle Scholar
  84. 83.
    Seiki M, Eddy R, Shows TB, Yoshida M. Nonspecific integration of the HTLV provirus genome into adult T-cell leukaemia cells. Nature 1984; 309:640–642.PubMedCrossRefGoogle Scholar
  85. 84.
    Grossman WJ, Kimata JT, Wong FH, Zutter M, Ley TJ, Ratner, L. Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I. Proc Natl Acad Sci USA 1995; 92:1057–1061.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2004

Authors and Affiliations

  • Gretchen L. Eiben
  • Diane M. Da Silva
  • Steven C. Fausch
  • Amanda M. Krier
  • I. Caroline Le Poole
  • Megan E. Papineau
  • Michael I. Nishimura
  • W. Martin Kast

There are no affiliations available

Personalised recommendations