Malignant Lymphoma in Cottontop Marmosets after Inoculation with Epstein-Barr Virus

Abstract

Neoplasia resembling human malignant lymphoma, reticulum cell Epstein-Barr virus (EBV) is regularly associated with lymphoproliferative disease. In infectious mononucleosis, a wide range of evidence suggests that the association is causal (1). In Burkitt lymphoma and nasopharyngeal carcinoma, EBV is associated with the tumor, and most patients with these diseases exhibit high titers of specific antibodies (2-4). EBV genome can be detected by nucleic acid hybridization in tumor-cell lines and in tumor biopsies in which viral particles are not found (5-6). Induction of experimental lymphoproliferative disease by EBV is essential, if the classical KochHenle postulates are to be fulfilled in identification of the agent responsible for these conditions. The investigations here described were undertaken with this requirement in mind.A significant biologic property of EBV is its capacity to cause human and certain other primate leukocytes to change into lymphoblastoid cell lines, which proliferate continuously in vitro (7-10). Immunosuppression. Half the animals in each experiment were given azathioprine (1 mg/day) and prednisilone (0.05 mg/day) intramuscularly. Inoculations were begun 3 days before administration of EBV and continued daily, except Sunday, for 3 weeks afterwards. The animals remained well during immunosuppressive therapy, and their leukocyte and platelet counts were stable.Virus Inoculations. Autologous EBV-transformed cells were washed and resuspended in Puck's saline A at a concentration of 1.2 to 3.0 X 108 cells per ml. The total inoculum for each animal was 1 ml, divided into 3 aliquots given intravenously, intraperitoneally, and subcutaneously. 1 ml of cellfree virus was inoculated similarly in other animals.Serology. The animals were bled weekly for 2 months and then biweekly. Sera were tested for EBV "viral capsid antibodies" by the indirect immunofluorescence method (18), with the B95-8 cell line as antigen and Raji cells, which do 2487

Isolation and sequencing of the Epstein-Barr virus BNLF-1 gene (LMP1) from a Chinese nasopharyngeal carcinoma

“…2b). B95-8 is a line of marmoset lymphocytes transformed with EBV type A from mononucleosis (Shope et al, 1973); Jijoye M 13 is an EBV-positive BL cell line carrying an EBV type B strain (Hinuma et al, 1967); DG75 is an EBV-negative BL line (Ben-Bassat et al, 1977); BJAB is a EBV-negative B cell lymphoma line (Menezes et al, 1975). Rhek-1 cells are human epidermal keratinocytes transformed by an adenovirus 12 (Adl2)-simian virus 40 (SV40) hybrid expressing SV40 large T and small t antigens, but not Adl2 E1A or E1B proteins (Rhim et al, 1985).…”

Simian homologues of Epstein–Barr virus

“…New World primates, e.g. cotton-top tamarins, inoculated with EBV developed either tumours or cleared the infection without establishing a persistent infection (Shope et al 1973). However, there was little evidence for successful experimental infection of various Old World species such as macaques or baboons when inoculated with B95-8 or P3HR-1 EBV strains (Frank et al 1976;Gerber et al 1969;Levine et al 1980).…”

A Cluster of Virus-Encoded MicroRNAs Accelerates Acute Systemic Epstein-Barr Virus Infection but Does Not Significantly Enhance Virus-Induced Oncogenesis In Vivo

“…Here, we utilized a humanized mouse model of EBV infection and tumorigenesis to examine the in vivo role of BHRF1 miRNAs. Until recently, in vivo studies with EBV have been limited; EBV exhibits very restricted species tropism (humans and New World primates such as the common marmoset and cottontop tamarin) (15,16). Humanized mice generated by transplanting CD34 ϩ hematopoietic stems cells into immune-deficient mice devoid of mouse lymphoid cells are systemically reconstituted with human myeloid and lymphoid cells, including human B cells (the primary target cell of EBV) (17).…”