Oncornavirus-like particles released from arginine-deprived human lymphoblastoid cell lines.

Abstract

TypeC RNA tumor virus particles were released from three different human lymphoblastoid cell lines after incubation in arginine-deficient medium. The released virus-like particles were characterized by (a) their ability to band in sucrose gradients at a density of 1.18-1.18 g/ml; (b) the presence of an RNA-directed DNA polymerase activity resembling that of the oncornaviruses; and (c) isolation of cores that and at a density of 1.26-1.27 g/ml in sucrose gradients. Examination of the arginine-deprived human lymphoblastoid cell line strain P3HR-1 by electron microscopy revealed the presence of C-type particdes in the intracellular spaces. The search for oncornaviruses associated with different forms of human cancer depends in most instances on the induction in vitro of the latent virus genomes present in the cancer cells. It has been demonstrated that arginine deprivation leads to the induction of oncornavirus synthesis in transformed cells (1-3). Rat cells transformed by the B77 strain of Rous sarcoma virus (RSV) released C-type particles into the medium when deprived of arginine (1). These particles were capable of transforming chick and rat cell cultures (M. Kotler, D. Boettiger, and R. Weiss, to be published). Incubation of leukocytes from patients with lymphatic leukemia in an arginine-deficient medium also resulted in the synthesis and release of C-type virus particles (2, 3). The spontaneous production of similar oncornavirus particles was demonstrated after short-term cultivation of leukemic bone-marrow cells (4, 5) in three myeloblastic cell lines from the peripheral blood of a patient with acute myelogenous leukemia (6) and from a human adenocarcinoma cell line (7).It was therefore of interest to determine the effect of arginine deficiency on lymphoblastoid cell lines. For

Evidence for type‐C retrovirus production by Burkitt's lymphoma‐derived cell line

“…The possibility that, in addition to Epstein-Barr virus (EBV), an RNA tumor virus might also play a role in the etiology of Burkitt's lymphoma has been suggested by earlier investigators who showed that this tumor contains RNA related to the RNA of a murine leukemia virus (Kufe et al, 1973a), and that at least a portion of this virus-related RNA exists in particles possessing physical and biochemical features characteristic of the RNA tumor viruses (Kufe et al, 1973b). Further substantiation of this notion was obtained from studies demonstrating that arginine deprivation of two Burkitt-lymphoma-derived cell lines, Raji and P3HR-1, activated them to release oncornavirus-like particles (Kotler et al, 1975).…”

Retrovirus-like particles in EBV-negative Burkitt's lymphoma cell line but not in EBV-DNA-positive lines from patients with ataxia telangiectasia and Down's syndrome

“…Note the irregularity and fragility of the particle membranes. (Kotler et al, 1975(Kotler et al, , 1977.…”

“…HUMAN lymphoid cells derived from lymphoma and leukaemia patients were found to contain retrovirus genetic information and to induce the formation of type C virus particles under suitable conditions (Gallagher & Gallo, 1975;Kotler et al, 1975;Mak et al, 1974;Nooter et al, 1975). Initial studies by Kotler et al (1973Kotler et al ( , 1975 showed that cultured lymphoblastoid cell lines from patients with leukaemia and Burkitt's lymphoma produce retrovirus-like particles after incubation in arginine-deficient medium.…”

“…In addition to containing EBV DNA, the BJAB-1-derived cell lines (GC/BJAB and AW/BJAB) retained their ability to produce retrovirus particles. In this respect the GC/BJAB lymphoblasts resemble Raji and P3HR-1 lymphoblasts, which carry EBV DNA in their nuclei and are capable of synthesizing a retrovirus when incubated in an arginine-deficient medium (Kotler et al, 1975(Kotler et al, , 1977 (Gelderblom et al, 1972) and in human neoplastic haemopoietic tissues (Popovic et al, 1974).…”

“…Initial studies by Kotler et al (1973Kotler et al ( , 1975 showed that cultured lymphoblastoid cell lines from patients with leukaemia and Burkitt's lymphoma produce retrovirus-like particles after incubation in arginine-deficient medium. These particles contain an endogenous reverse-transcriptase activity that is stimulated by the addition of exogenous templates such as oligo (dG).poly(rC) or oligo(dT).poly(rA).…”