Primate type-C virus nucleic acid sequences (woolly monkey and baboon types) in tissues from a patient with acute myelogenous leukemia and in viruses isolated from cultured cells of the same patient

Abstract

Cultured peripheral blood leukocytes from a woman (patient HL23) with acute myelogenous leukemia produced type-C RNA tumor viruses (HL23V). The viruses were analyzed by molecular hybridization experiments after transmission to five secondary cell culture lines. Using the criteria of molecular hybridization, we concluded that all of the transmitted virus isolates have nucleotide sequences related to the genome of simian sarcoma virus (SiSV). In addition, in agreement with data reported elsewhere, some of the transmitted viruses also have nucleotide sequences related to those of the baboon endogenous virus (BaEV). We also used molecular hybridization to ascertain whether both viruses could have originated from the patient HL23. Utilizing [3H] cDNA complementary to RNA from the separated BaEV-related component of HL23V and hybridizing this cDNA to DNA from tissues of the patient, we detected sequences related to BaEV in DNA obtained from the patient's spleen. These BaEV DNA sequences were also detectable when 125I-labeled RNA from BaEV was used as a probe. In agreement with earlier results, however, no SiSV-related sequences were detectable in the DNA of her tissues. Cytoplasmic viral-like particles, which had a buoyant density of 1.15-1.2 g/ml and were capable of synthesizing cDNA in association with a 35S RNA in vitro, were also found in the patient's fresh uncultured leukemic blood cells. cDNA synthesized by the cytoplasmic particles contained some sequences that hybridized to RNA from SiSV and, in addition, some that hybridized to RNA from BaEV. The cDNA also hybridized significantly to DNA isolated from the spleen of patient HL23 and to cytoplasmic RNA from the patient's leukocytes. These molecular hybridization results with nucleic acids obtained from the fresh blood cells of the patient, combined with the repeated isolation of similar viruses from different blood and bone marrow samples from the same patient, suggest that the virus come directly from the leukemic cell samples. The finding of BaEV-related DNA proviral sequences in the spleen of the patient strongly supports this interpretation. The failure so far to find a complete SiSV-related provirus is perplexing, but could be attributable to the existence of such a provirus in DNA of only a small population of cells in most leukemic patient.