Molecular Biology of Human T-Cell Leukemia Virus Associated with Adult T-Cell Leukemia

  • Mitsuaki Yoshida
  • Seisuke Hattori
  • Motoharu Seiki
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 115)


Many retroviruses have been isolated from various species of animals and these have provided useful systems for studying the mechanisms of tumorigenesis; a number of viral onc genes and the corresponding cellular proto-onc genes that have been conserved during evolution have been identified (Vogt 1977; Bishop 1982). From the studies of these viruses and protoonc genes, general mechanisms of tumorigenesis have been proposed (Hayward et al. 1981; Weinberg 1982). Based on these recent developments, it now seems likely that human retroviruses will provide helpful information for molecular analysis of cellular transformation in the human system. However, until recently, human retroviruses were not well characterized, although many preliminary observations have been reported.


Primary Tumor Cell Provirus Genome Provirus Sequence Fresh Leukemic Cell Nonleukemic Cell 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Benveren CV, Straaten FV, Galleshaw JA, Verma I (1981) Nucleotide sequence of the genome of a murine sarcoma virus. Cell 27: 97–108CrossRefGoogle Scholar
  2. Benz EW Jr, Wydro RM, Nadel-Ginard B, Dina D (1981) Moloney murine sarcoma pro viral DNA is a transcriptional unit. Nature 288: 665–669CrossRefGoogle Scholar
  3. Bishop JM (1982) Oncogenes. Sei Am 246: 68 - 78Google Scholar
  4. Blattner WA, Kalyanaraman VS, Robert-Guroff M, Lister A, Galton DAG, Sarin PS, Crawford MH, Catovsky D, Greaves M, Gallo RC (1982) The human type C retrovirus, HTLV, in blacks from the Caribbean region, and relationship to adult T cell leukemia/lymphoma. Int J Cancer 30: 257–264PubMedCrossRefGoogle Scholar
  5. Blattner WA, Gibbs WN, Saxinger C, Robert-Guroff M, Clark J, Lofters W, Hanchard B, Campbell M Gallo RC (1983) Human T cell leukemia/lymphoma virus-associated lymphoreticular neoplasia in Jamaica. Lancet 2: 61PubMedCrossRefGoogle Scholar
  6. Chen R (1982) Complete amino acid sequence and glycosylation sites of glycoprotein gp70 of Friend murine leukemia virus. Proc Natl Acad Sei USA 79: 5788–5792CrossRefGoogle Scholar
  7. Copeland TD, Oroszlan S, Kalyanaraman VS, Sarngadharan MG, Gallo RC (1983) Complete animo acid sequence of human T cell leukemia virus structural protein pl5. FEBS Lett, 162: 390–395PubMedCrossRefGoogle Scholar
  8. Essex M, Mclane MF, Lee TH, Falk L, Howe CWS, Mullins JI, Cabradilla C, Francis DP (1983) Antibodies to cell membrane antigens associated with human T-cell leukemia virus in patients with AIDS. Science 20: 859–862CrossRefGoogle Scholar
  9. Hattori S, Imagawa K, Shimizu F, Hashimura E, Seiki M, Yoshida M (to be published) Identification of envelope glycoprotein encoded by env gene of human retrovirus HTLV. GanGoogle Scholar
  10. Hattori S, Kiyokawa T, Imagawa K, Shimizu F, Hashimura E, Seiki M, Yoshida M (1984) Identification of gag and env gene products of human T-cell leukemia virus (HTLV). Virology 136: 338–347PubMedCrossRefGoogle Scholar
  11. Hayward WS, Neel BG, Astrin SM (1981) Activation of a cellular onc gene by promotor insertionin ALV-induced lymphoid leukosis. Nature 290: 475–480PubMedCrossRefGoogle Scholar
  12. Hinuma Y, Nagata K, Misoka M, Nakai M, Matsumoto T, Kinoshita K, Shirakawa S, Miyoshi I (1981) Adult T cell leukemia: Antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sei USA 78: 6476–6480CrossRefGoogle Scholar
  13. Hinuma Y, Komoda H, Chose T, Kondo T, Kohakura M, Takenaka T, Kikuchi M, Ichimaru M, Yunoki K, Sato M, Matsuo R, Takiuchi Y, Uchino H, Hanaoka M (1982) Antibodies to adult T cell leukemia virus associated antigen (ATLA) in sera from patients with ATL and controls in Japan: A nation-wide sero-epidemiologic study. Int J Cancer 29: 631–635PubMedCrossRefGoogle Scholar
  14. Kalyanaraman VS, Sarngadharan MG, Nakao Y, Ito Y, Aoki T, Gallo RC (1982) Natural antibodies to the structural core protein (p24) of the human T cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan. Proc Natl Acad Sei USA 79: 1653–1657CrossRefGoogle Scholar
  15. Kiyokawa T, Seiki M, Imagawa K, Shimizu F, Yoshida M (1984) Identification of a protein (p40x) encoded by a unique sequence pX of HTLV-I. Gann (Jpn J Cancer Res) 75: 747–751Google Scholar
  16. Miyoshi I, Kubonishi I, Sumida M, Hiraki S, Kimura I, Miyamoto K, Sato J (1980) A novel T cell line derived from adult T cell leukemia. Gann (Jpn J Cancer Res) 71: 155–156Google Scholar
  17. Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Ohtsuki Y, Shiraishi Y, Nagata K, Hinuma Y (1981) Type C virus particles in a cord T cell line derived by cocultivating normal human cord leukocytes and human leukemic T cells. Nature 294: 770–771PubMedCrossRefGoogle Scholar
  18. Nüsse R, Varmus HE (1982) Many tumors induced by the mouse mammary tumor virus contain a pro virus integrated in the same region of the host genome. Cell 31: 99–109PubMedCrossRefGoogle Scholar
  19. Oroszlan S, Sarngadharan MG, Copeland TD, Kalyanaraman VS, Gilden RV, Gallo RC (1982) Primary strueture analysis of the major internal protein p24 of human type C T cell leukemia virus. Proc Natl Acad Sei USA 79: 1291–1294CrossRefGoogle Scholar
  20. Philipson L, Andersonn P, Olshevsky V, Weinberg RA, Baltimore D (1978) Translation of MuLV and MSV RNAs in nuclease-treated reticulocyte extract: Enhancement of the gag/pol polypeptide with yeast suppressor tRNA. Cell 13: 189–199PubMedCrossRefGoogle Scholar
  21. Poiesz BJ, Ruscetti.FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC (1980) Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T cell lymphoma. Proc Natl Acad Sei USA 77: 7415–7419Google Scholar
  22. Popovic M, Reitz MS, Sarngadharan MG, Robert-Guroff M, Kalyanaraman VS, Nakao Y, Miyoshi I, Minowada J, Yoshida M, Ito Y, Gallo RC (1982) The virus of Japanese adult T cell leukemia is a member of the human T cell leukemia virus group. Nature 300: 63–66PubMedCrossRefGoogle Scholar
  23. Rho HM, Poiesz B, Rusetti FW, Gallo RC (1981) Characterization of the reverse transcriptase from a new retrovirus (HTLV) produced by a human cutaneous T-cell lymphoma cell line. Virology 112: 355–360PubMedCrossRefGoogle Scholar
  24. Robert-Guroff M, Nakao Y, Notake K, Ito Y, Sliski A, Gallo RC (1982) Natural antibodies to human retrovirus HTLV in a Cluster of Japanese patients with adult T cell leukemia. Science 215: 975–978PubMedCrossRefGoogle Scholar
  25. Schupback JD, Kalyanaraman VS, Sarngadharan MG, Blattner WA, Gallo RC (1983) Antibodies against three purified proteins of the human type C retrovirus, human T cell leukemia/lymphoma virus, in adult T cell leukemia lymphoma patients and healthy blacks from the Caribbean. Cancer Res 43: 886–891Google Scholar
  26. Schwartz DE, Tizard R, Gilbert W (1983) The nucleotide sequence of Rous sarcoma virus. Cell 32: 853–869PubMedCrossRefGoogle Scholar
  27. Seiki M, Hattori S, Yoshida M (1982) Human adult T cell leukemia virus: Molecular cloning of the provirus DNA and the unique terminal strueture. Proc Natl Acad Sei USA 79: 6899–6902CrossRefGoogle Scholar
  28. Seiki M, Hattori S, Hirayama Y, Yoshida M (1983) Human adult T cell leukemia virus: Complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sei USA 80: 3618–3622CrossRefGoogle Scholar
  29. Seiki M, Eddy R, Sows TB, Yoshida M (1984) Nonspecific integration of the HTLV provirus genome into adult T-cell leukemia cells. Nature 309: 640–642PubMedCrossRefGoogle Scholar
  30. Shinnick TM, Lernner RA, Sutcliffe JG (1984) Nucleotide sequence of Moloney murine leukemia virus. Nature 293: 543–648CrossRefGoogle Scholar
  31. Tajima K, Tominaga S, Suchi T, Kawagoe T, Komoda H, Hinuma Y, Oda T, Fujita K (1982) Epidemiological analysis of the distribution of antibody to adult T cell leukemia virus-associated antigen: possible horizontal transmission of adult T cell leukemia virus. Gan 73: 893–901PubMedGoogle Scholar
  32. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H (1977) Adult T cell leukemia: Clinical and hematological features of 16 cases. Blood 50: 481–491PubMedGoogle Scholar
  33. Varmus HE (1982) Form and function of retro viral pro viruses. Science 216:812-820 Vogt PK (1977) Genetics of RNA tumor viruses. Compr Virol 10: 341–455Google Scholar
  34. Vogt PK (1977) Genetics of RNA tumor viruses. Compr Virol 10:341–455Google Scholar
  35. Watanabe T, Seiki M, Yoshida M (1984) ATLV (Japanese isolate) and HTLV type I (US isolate) are the same strain of retrovirus. Virology 133: 238–241PubMedCrossRefGoogle Scholar
  36. Weinberg RA (1982) Oncogenes of spontaneous and chemically induced tumors. Adv Cancer Res 36: 149–163PubMedCrossRefGoogle Scholar
  37. Weiss SR, Hackett PB, Oppermann H, Ullrich A, Levinthow L, Bishop JM (1978) Cell free translation of avian sarcoma virus RNA: Suppression of the gag termination codon does not augment synthesis of the joint gag!pol product. Cell 15: 607–614PubMedCrossRefGoogle Scholar
  38. Wong-Staal F, Hahn H, Manzari V, Colonbini S, Franchini G, Gelman EP, Gallo RC (1983) A survey of human leukemias for sequence of a human retrovirus. Nature 302: 626–628PubMedCrossRefGoogle Scholar
  39. Yamamoto N, Schneider J, Hinuma Y, Hunsmann G (1982) Adult T-cell leukemia assoiated antigen (ATLA): Detection of a glycoprotein in cell- and virus-free supernatant. Z Naturforsch 37c:731– 732Google Scholar
  40. Yamamoto N, Hinuma Y, Hausen HZ, Schneider J, Hunsmann G (1983) African green monkeys are infected with adult T-cell leukemia virus or a closely related agent. Lancet 1: 240–241PubMedCrossRefGoogle Scholar
  41. Yoshida M (1983) Human leukemia virus associated with adult T-cell leukemia (ATL). Gann (Jpn J Cancer Res) 74: 777–789Google Scholar
  42. Yoshida M, Miyoshi I, Hinuma Y (1982) Isolation and characterization of retrovirus from cell lines of human adult T cell leukemia and its implieation in the disease. Proc Natl Acad Sei USA 79: 2031–2035CrossRefGoogle Scholar
  43. Yoshida M, Seiki M, Hattori S, Watanabe T (1984) Genome structure of HTLV and its involvement in the development of adult T-cell leukemia (ATL). In: Gallo RC, Essex M, Topp W (eds) Human T-cell leukemia/lymphoma viruses. Cold Spring Harbor Laboratory, New York p 141–148Google Scholar
  44. Yoshida M, Seiki M, Yamaguchi K, Takatsuki K (1984) Monoclonal integration of human T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggests causative role of human T-cell leukemia virus in the disease. Proc Natl Acad Sei USA 81: 2534–2537CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1985

Authors and Affiliations

  • Mitsuaki Yoshida
    • 1
  • Seisuke Hattori
    • 1
  • Motoharu Seiki
    • 1
  1. 1.Department of Viral OncologyCancer InstituteKami-Ikebukuro, Toshima-ku, TokyoJapan

Personalised recommendations