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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1994 Aug;85(8):808–818. doi: 10.1111/j.1349-7006.1994.tb02952.x

HTLV‐II Non‐integrated Malignant Lymphoma Induction in Japanese White Rabbits Following Intravenous Inoculation of HTLV‐II‐infected Simian Leukocyte Cell Line (Si‐IIA)

Kazuhiko Hayashi 1,✉, Nobuya Ohara 1, Tirtha Raj Koirala 1, Hideo Ino 1, Hong Li Chen 1, Norihiro Teramoto 1, Eisaku Kondo 1, Tadashi Yoshino 1, Kiyoshi Takahashi 1, Masao Yamada 2, Noriko Tomita 3, Kanji Miyamoto 4, Koji Fujimoto 5, Yasuhiro Yoshikawa 5, Tadaatsu Akagi 1
PMCID: PMC5919558  PMID: 7928626

Abstract

Lymphoma induction in rabbits by an unknown factor derived from an HTLV‐II‐producing simian (Cynomolgus) leukocyte cell line (Si‐IIA) is reported. Thirteen of 17 male Japanese white rabbits (76%) inoculated intravenously with Si‐IIA cells developed malignant lymphoma including Hodgkin‐like lymphoma between 62 and 167 days after inoculation. Historically, there was extensive diffuse or nodular infiltration of either large cell type or mixed type lymphoma cells in many organs, frequently involving the spleen, liver, lymph nodes and kidneys, and less frequently the thymus, bone marrow, lungs, heart, skin and gastrointestinal tract. Hodgkin‐like lymphoma was also observed in two rabbits. Chromosomal analysis of five cell lines established from tumor‐bearing rabbits revealed the male rabbit karyotype. The immunophenotype of these tumor cells was usually T‐cell (CD5+or, r RT1+, RT2+or‐, CD45+, CD4−, RABELA− and MHC class II‐DQ+) except for Hodgkin‐like lymphoma cells which expressed only CD45. However, integration of the HTLV‐II provirus genome could not be demonstrated in the tumor tissues or any of the rabbit cell lines by polymerase chain reaction or Southern blot analysis. Moreover, no lymphoma was induced by inoculation of HTLV‐IIC, MOT (other HTLV‐II‐producing human cell lines) or TALL‐1 (control). Two of four rabbits injected with cell‐free pellets from Si‐IIA cultures died of malignant lymphoma (15‐20 days). Five irradiated rabbit cell lines were inoculated but only one (Ra‐SLN) induced lymphoma in 1 of 3 rabbits at 27 days. Neither Herpesvirus saimiri nor Herpesvirus ateles (simian oncogenic viruses) was detected in Si‐IIA cells by immunofluorescence testing. These data suggest that the high rate of lymphoma induction in rabbits may be caused not by only HTLV‐II or well known simian oncogenic viruses, but rather by an unknown passenger agent derived from Si‐IIA or HTLV‐IIA, with which Si‐IIA was established.

Keywords: Malignant lymphoma, Rabbit, Simian leukocyte, HTLV‐II

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REFERENCES

  • 1. ) Kalyanaraman , V. S. , Sarngadharan , M. G. , Robert‐Guroff , M. , Miyoshi , I. , Blayney , D. , Golde , D. and Gallo , R. C.A new subtype of human T‐cell leukemia virus (HTLV‐II) associated with a T‐cell variant of hairy cell leukemia . Science , 218 , 571 – 573 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Rosenblatt , J. D. , Golde , D. W. , Wachsman , W. , Giorgi , J. V. , Jacobs , A. , Schmidt , G. M. , Quan , S. , Gasson , J. C. and Chen , I. S. Y.A second isolate of HTLV‐II associated with atypical hairy‐cell leukemia. JV . Engl. J. Med. , 315 , 372 – 377 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Kalyanaraman , V. S. , Narayanan , R. , Feorino , P. , Ramsey , R. B. , Palmer , E. L. , Chorda , T. , McDougal , S. , Getchell , J. P. , Holloway , B. , Harrison , A. K. , Cabradilla , C. D. , Telfer , M. and Evatt , B.Isolation and characterization of a human T cell leukemia virus type II from a hemophilia‐A patient with pancytopenia . EMBO J. , 4 , 1455 – 1460 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. ) Lee , H. , Swanson , P. , Shorty , V. S. , Zack , J. A. , Rosenblatt , J. D. and Chen , I. S. Y.High rate of HTLV‐II infection in seropositive IV drug abusers in New Orleans . Science , 244 , 471 – 475 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Page , J. B. , Lai , S. , Chitwood , D. D. , Klimas , N. G. , Smith , P. C. and Fletcher , M. A.HTLV‐I/II sero‐positivity and death from AIDS among HIV‐I seropositive intravenous drug users . Lancet , 335 , 1439 – 1441 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Kira , J. , Koyanagi , Y. , Hamamado , T. , Itoyama , Y. , Yamamoto , N. and Goto , I.HTLV‐II in patients with HTLV‐I‐associated myelopathy . Lancet , 338 , 64 – 65 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Ijichi , S. , Zaninovic , V. , Leon‐ , S. F. E. , Katahira , Y. , Sonoda , S. , Miura , T. , Hayami , M. and Hall , W. W.Identification of human T cell leukemia virus type IIb infection in the Wayu, an aboriginal population of Colombia . Jpn. J. Cancer Res. , 84 , 1215 – 1218 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. ) Loughran , T. P. , Jr. , Coyle , T. , Sherman , M. P. , Starkebaum , G. , Ehrlich , G. D. , Ruscetti , F. W. and Poiesz , B. J.Detection of human T‐cell leukemia/lym‐phoma virus, type II, in a patient with large granular lymphocyte leukemia . Blood , 80 , 1116 – 1119 ( 1992. ). [PubMed] [Google Scholar]
  • 9. ) Zucker‐Franklin , D. , Hooper , W. C. and Evatt , B. L.Human lymphotropic retroviruses associated with mycosis fungoides: evidence that human T‐cell lymphotropic virus type II (HTLV‐II) as well as HTLV‐I may play a role in the disease . Blood , 80 , 1537 – 1545 ( 1992. ). [PubMed] [Google Scholar]
  • 10. ) Miyamoto , K. , Tomita , N. , Ohtsuki , Y. and Kitajima , K.Detection of provirus in an HTLV‐II producer CD8 + T cell line by polymerase chain reaction combined with digoxigenin‐ELISA method . Jpn. J. Cancer Res. , 81 , 313 – 316 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. ) Miyamoto , K. , Tomita , N. , Hayashi , K. , Ohara , N. , Akagi , T. , Ohtsuki , Y. , Goda , N. , Shirai , K. , Okazaki , Y. and Kitajima , K.Isolation of HTLV‐II and establishment of HTLV‐II transformed T‐cell lines having subtype a . Igakunoayumi , 164 , 657 – 658 ( 1993. )( in Japanese ). [Google Scholar]
  • 12. ) Miyamoto , K. , Tomita , N. , Hayashi , K. and Akagi , T.Transformation of animal cells with human T‐cell leukemia virus type II . Jpn, J. Cancer Res. , 81 , 720 – 722 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. ) Hayashi , K. , Ohara , N. , Fujiwara , K. , Aoki , H. , Jeon , H. J. , Takahashi , K. , Tomita , N. , Miyamoto , K. and Akagi , T.Co‐expression of CD4 and CDS associated with elevated interleukin‐4 in a cord T cell line derived by coculturing normal human cord leukocytes and an HTLV‐II‐producing simian leukocyte cell line (Si‐IIA) . J.Cancer Res. Clin. Oncol , 119 , 137 – 141 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Ohara , N. , Hayashi , K. , Miyamoto , K. , Tomita , N. , Fujiwara , K. , Kondo , E. , Takahashi , K. , Ohtsuki , Y. and Akagi , T.A human T cell line with an abnormal trisomy 2 karyotype established by coculture of peripheral lymphocytes with an HTLV‐II‐infected simian leukocyte cell line . Acta Pathol Jpn. , 43 , 237 – 243 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Hayashi , K. , Ohara , N. , Fujiwara , K. , Jeon , H. J. , Koirala , T. R. , Takahashi , K. , Akagi , T. , Tomita , N. and Miyamoto , K.HTLV‐II‐specific antisera raised in rabbits immunized with a synthetic peptide of HTLV‐II envelope protein . Virchows Arch. B , 63 , 37 – 41 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Ohara , N. , Hayashi , K. , Takahashi , K. , Miyamoto , K , and Akagi , T.A novel monoclonal antibody specifically reactive with human T‐lymphotropic virus type‐II (HTLV‐II) envelope protein . Int. J, Cancer , 54 , 858 – 861 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Miyamoto , K. , Tomita , N. , Ishii , A. , Nonaka , H. , Kondo , T. , Tanaka , T. and Kitajima , K.Chromosome abnormalities of leukemic cells in adult patients with T‐cell leukemia . J. Natl. Cancer Inst. , 73 , 353 – 362 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Shimotohno , K. , Takahashi , Y. , Shimizu , N. , Gojobori , T. , Golde , D. W. and Chen , I. S. Y.Complete nucleotide sequence of an infectious clone of human T‐cell leukemia virus type II: an open reading frame for the protease gene , Proc. Natl. Acad. Sci. USA , 82 , 3101 – 3105 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Cockerell , G. L. , Weiser , M. G. , Rovnak , J. , Wicks‐Beard , B. , Roberts , B. , Post , A. , Chen , I. S. Y. and Lairmore , M. D.Infectious transmission of human T‐cell lympho‐ tropic virus type II in rabbits . Blood , 78 , 1532 – 1537 ( 1991. ). [PubMed] [Google Scholar]
  • 20. ) Fleckenstein , B. and Desrosiers , R. C.Herpesvirus saimiri and Herpesvirus ateles . In “Herpesviruses,” Vol.1 , ed. Roizman B. , pp. 253 – 331 ( 1982. ). Plenum Press; , New York and London . [Google Scholar]
  • 21. ) Fujimoto , K. , Terato , K. , Miyamoto , J. , Ishiko , H. , Fujisaki , M. , Cho , F. and Honjo , S.Establishment of a B‐lymphoblastoid cell line infected with Epstein‐Barr‐related virus from a cynomolgus monkey (Macaco fascicularis) . J. Med. Primatol. , 19 , 21 – 30 ( 1990. ). [PubMed] [Google Scholar]
  • 22. ) Hayami , M.Simian T‐cell leukemia virus (STLV‐I) ‐ HTLV‐I‐related virus in non‐human primates . Gann Monogr. Cancer Res. , 39 , 247 – 256 ( 1992. ). [Google Scholar]
  • 23. ) Miyamoto , K. , Kamiya , T. , Minowada , J. , Tomita , N. and Kitajima , K.Transformation of CD8 + T‐cells producing a strong cytopathic effect on CD4+ T‐cells through syn‐cytium formation by HTLV‐II . Jpn. J. Cancer Res. , 82 , 1178 – 1183 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

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