Malignant lymphoma induction in rabbits by intravenous inoculation of Epstein-Barr-virus-related herpesvirus from HTLV-II-transformed cynomolgus leukocyte cell line (Si-IIA).

K. Hayashi, T. R. Koirala, Hideo Ino, H. L. Chen, N. Ohara, N. Teramoto, Tadashi Yoshino, K. Takahashi, Masao Yamada, S. Nii

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Abstract

Malignant lymphomas, which were usually of T-cell type, were induced in 10 of 13 (77%) male rabbits (Japanese white, 8/10; New Zealand white, 2/3) inoculated i.v. with HTLV-II-transformed simian (Cynomolgus) leukocyte cell line (Si-IIA) cells. Of 7 rabbits injected with cell-free pellets from Si-IIA cultures, 5 also developed malignant lymphoma (15-28 days). Lymphoma development was completely inhibited by inactivation of cell-free pellets from Si-IIA culture with ethyl ether and was almost suppressed by neutralization of the cell-free pellets with anti-Si-IIA sera. Herpesvirus particles were discovered very rarely in Si-IIA cells, in addition to C-type virus particles, by electron microscopy. Si-IIA cells were positive for Epstein-Barr-virus (EBV)-associated nuclear antigen (EBNA) by immunofluorescence (IF) test. Antibody response to viral capsid antigen of EBV was also detected in sera from rabbits inoculated with Si-IIA. EBV-encoded RNA-1 (EBER-1) was demonstrated in Si-IIA, the tumor tissues and all rabbit tumor cell lines by in situ hybridization. EBV DNA was also detected in Si-IIA and rabbit lymphoma cell lines by polymerase chain reaction (PCR) and Southern blotting. However, EBV DNA was amplified only by some primers complementary to human EBV sequence (B95-8), but not by other primers. Integration of HTLV-II provirus genome could not be detected in Si-IIA-induced rabbit tumor cells. Moreover, no lymphoma was induced by inoculation of HTLV-IIC and MOT (other HTLV-II-producing human cell lines), B95-8(EBV-producing cell line) or TALL-1 and peripheral leukocytes from normal Cynomolgus (controls). Neither Herpesvirus saimiri nor H. ateles (simian oncogenic viruses) were detected in Si-IIA cells by IF test. These data suggest that the high rate of lymphoma induction in rabbits may not be caused by HTLV-II, human EBV (B95-8) or well-known simian oncogenic viruses, but by EBV-related herpesvirus derived from Si-IIA cells or HTLV-IIA cells, with which Si-IIA was established. The availability of this animal model promises to clarify the role of EBV in human lymphoma and provides a means of studying prophylactic and therapeutic regimens.

Original languageEnglish
Pages (from-to)872-880
Number of pages9
JournalInternational Journal of Cancer
Volume63
Issue number6
Publication statusPublished - Dec 11 1995

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Human T-lymphotropic virus 2
Herpesviridae
Human Herpesvirus 4
Lymphoma
Leukocytes
Rabbits
Cell Line
Oncogenic Viruses
Fluorescent Antibody Technique
Atelinae
Saimiriine Herpesvirus 2
Epstein-Barr Virus Nuclear Antigens
Proviruses
Viral Antigens
Capsid
DNA
Southern Blotting
Tumor Cell Line
Serum
New Zealand

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Malignant lymphoma induction in rabbits by intravenous inoculation of Epstein-Barr-virus-related herpesvirus from HTLV-II-transformed cynomolgus leukocyte cell line (Si-IIA). / Hayashi, K.; Koirala, T. R.; Ino, Hideo; Chen, H. L.; Ohara, N.; Teramoto, N.; Yoshino, Tadashi; Takahashi, K.; Yamada, Masao; Nii, S.

In: International Journal of Cancer, Vol. 63, No. 6, 11.12.1995, p. 872-880.

Research output: Contribution to journalArticle

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abstract = "Malignant lymphomas, which were usually of T-cell type, were induced in 10 of 13 (77{\%}) male rabbits (Japanese white, 8/10; New Zealand white, 2/3) inoculated i.v. with HTLV-II-transformed simian (Cynomolgus) leukocyte cell line (Si-IIA) cells. Of 7 rabbits injected with cell-free pellets from Si-IIA cultures, 5 also developed malignant lymphoma (15-28 days). Lymphoma development was completely inhibited by inactivation of cell-free pellets from Si-IIA culture with ethyl ether and was almost suppressed by neutralization of the cell-free pellets with anti-Si-IIA sera. Herpesvirus particles were discovered very rarely in Si-IIA cells, in addition to C-type virus particles, by electron microscopy. Si-IIA cells were positive for Epstein-Barr-virus (EBV)-associated nuclear antigen (EBNA) by immunofluorescence (IF) test. Antibody response to viral capsid antigen of EBV was also detected in sera from rabbits inoculated with Si-IIA. EBV-encoded RNA-1 (EBER-1) was demonstrated in Si-IIA, the tumor tissues and all rabbit tumor cell lines by in situ hybridization. EBV DNA was also detected in Si-IIA and rabbit lymphoma cell lines by polymerase chain reaction (PCR) and Southern blotting. However, EBV DNA was amplified only by some primers complementary to human EBV sequence (B95-8), but not by other primers. Integration of HTLV-II provirus genome could not be detected in Si-IIA-induced rabbit tumor cells. Moreover, no lymphoma was induced by inoculation of HTLV-IIC and MOT (other HTLV-II-producing human cell lines), B95-8(EBV-producing cell line) or TALL-1 and peripheral leukocytes from normal Cynomolgus (controls). Neither Herpesvirus saimiri nor H. ateles (simian oncogenic viruses) were detected in Si-IIA cells by IF test. These data suggest that the high rate of lymphoma induction in rabbits may not be caused by HTLV-II, human EBV (B95-8) or well-known simian oncogenic viruses, but by EBV-related herpesvirus derived from Si-IIA cells or HTLV-IIA cells, with which Si-IIA was established. The availability of this animal model promises to clarify the role of EBV in human lymphoma and provides a means of studying prophylactic and therapeutic regimens.",
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T1 - Malignant lymphoma induction in rabbits by intravenous inoculation of Epstein-Barr-virus-related herpesvirus from HTLV-II-transformed cynomolgus leukocyte cell line (Si-IIA).

AU - Hayashi, K.

AU - Koirala, T. R.

AU - Ino, Hideo

AU - Chen, H. L.

AU - Ohara, N.

AU - Teramoto, N.

AU - Yoshino, Tadashi

AU - Takahashi, K.

AU - Yamada, Masao

AU - Nii, S.

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N2 - Malignant lymphomas, which were usually of T-cell type, were induced in 10 of 13 (77%) male rabbits (Japanese white, 8/10; New Zealand white, 2/3) inoculated i.v. with HTLV-II-transformed simian (Cynomolgus) leukocyte cell line (Si-IIA) cells. Of 7 rabbits injected with cell-free pellets from Si-IIA cultures, 5 also developed malignant lymphoma (15-28 days). Lymphoma development was completely inhibited by inactivation of cell-free pellets from Si-IIA culture with ethyl ether and was almost suppressed by neutralization of the cell-free pellets with anti-Si-IIA sera. Herpesvirus particles were discovered very rarely in Si-IIA cells, in addition to C-type virus particles, by electron microscopy. Si-IIA cells were positive for Epstein-Barr-virus (EBV)-associated nuclear antigen (EBNA) by immunofluorescence (IF) test. Antibody response to viral capsid antigen of EBV was also detected in sera from rabbits inoculated with Si-IIA. EBV-encoded RNA-1 (EBER-1) was demonstrated in Si-IIA, the tumor tissues and all rabbit tumor cell lines by in situ hybridization. EBV DNA was also detected in Si-IIA and rabbit lymphoma cell lines by polymerase chain reaction (PCR) and Southern blotting. However, EBV DNA was amplified only by some primers complementary to human EBV sequence (B95-8), but not by other primers. Integration of HTLV-II provirus genome could not be detected in Si-IIA-induced rabbit tumor cells. Moreover, no lymphoma was induced by inoculation of HTLV-IIC and MOT (other HTLV-II-producing human cell lines), B95-8(EBV-producing cell line) or TALL-1 and peripheral leukocytes from normal Cynomolgus (controls). Neither Herpesvirus saimiri nor H. ateles (simian oncogenic viruses) were detected in Si-IIA cells by IF test. These data suggest that the high rate of lymphoma induction in rabbits may not be caused by HTLV-II, human EBV (B95-8) or well-known simian oncogenic viruses, but by EBV-related herpesvirus derived from Si-IIA cells or HTLV-IIA cells, with which Si-IIA was established. The availability of this animal model promises to clarify the role of EBV in human lymphoma and provides a means of studying prophylactic and therapeutic regimens.

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