Murine Mammary Tumor Virus Research Articles

Specific inhibition of mammalian ribonucleic acid C-type virus deoxyribonucleic acid polymerases by rat antisera.

Inhibition of the ribonucleic acid (RNA)- and deoxyribonucleic acid (DNA)-dependent DNA polymerase activities of mammalian C-type viruses was obtained with sera from rats bearing murine leukemia virus-induced transplant tumors. Polymerase activities of nonmammalian (viper) C-type virus and murine mammary tumor virus were not inhibited by such sera nor by serum from a rat immunized with the DNA polymerase of feline leukemia virus purified by isoelectric focusing. The latter serum appeared to inhibit preferentially the DNA-dependent DNA polymerase activity of mammalian C-type viruses showing no inhibition of RNA-dependent DNA synthesis.

Helical nucleocapsid structure of the oncogenic ribonucleic acid viruses (oncornaviruses).

Negative staining of virions and isolated nucleoids from avian myeloblastosis virus, murine leukemia virus, murine mammary tumor virus, and feline leukemia virus reveals common internal structures. The majority of virions that are penetrated by phosphotungstate show spherical nucleoids with no apparent symmetry. In a small percentage of virions, two distinctive structures are found: (i) single strands (3 to 5 nm in diameter) which are presumed to be the nucleoprotein and are found randomly oriented throughout the viral interior and (ii) helical structures (7 to 9 nm in diameter) which contain these nucleoprotein strands and are observed at the periphery of the nucleoid. The finding of helical nucleocapsid segments at the periphery of the nucleoid, as well as the hollow spherical structure observed in thin section of budding virions, has led to the hypothesis that the nucleocapsid of the freshly budded oncornavirus is supercoiled as a hollow sphere. This symmetry, however, is considered transient, as the internal structure of the extracellular virus undergoes a conformational rearrangement; thus, due to structural instability, the nucleocapsid uncoils and the nucleoprotein strands fill the interior of the virion. The extracellular virion is therefore considered degenerate in respect to symmetry, explaining the difficulty in detecting a helical nucleocapsid.

The Internal Structure of the Oncogenic RNA Viruses

Negative staining technique with potassium phosphotungstate (pH 7.0) was used to study the internal structure of the avian myeloblastosis virus, murine leukemia virus, murine mammary tumor virus and feline leukemia virus. Two essential structural features of the viral interior were observed: 1) single strands (30-50 A° in diameter) randomly oriented to give the appearance of a ball of yarn inside the virion; and 2) paired strands (70-90A° in diameter) that appear to be double helices which upon uncoiling give the single strands. Figs. 1 and 2 show the morphology of type B, and C particles respectively, where helical structures in the interior of the virions can be seen (arrow). The subunit structures observed on the helical regions are morphologically similar to those seen on the surface of the nucleoid that do not show helical symmetry. When helical segments were observed in the virus they were almost always seen at the periphery of the nucleoid. This is in agreement with the hollow spherical nucleoid structure of budding virions seen in thin section and suggests that the nucleocapsid is supercoiled as a hollow sphere.

Ultrastructural comparison of a virus from a Rhesus-monkey mammary carcinoma with four oncogenic RNA viruses.

The ultrastructure and morphogenesis of Mason-Pfizer monkey virus, isolated from a mammary carcinoma in a Rhesus monkey, was compared with those of murine mammary tumor virus, murine leukemia virus, L1210 leukemia-associated virus, and avian myeloblastosis virus. The simian virus resembled murine mammary tumor virus and the L1210 virus in that it produced intracytoplasmic particles that were enveloped during budding. It resembled L1210 virus and murine leukemia virus in budding with smooth envelopes. It differed from all the others in being more fragile. These similarities, combined with biochemical characteristics reported elsewhere in this issue, suggest that the monkey virus is an oncogenic RNA virus.

Neutralization of murine mammary tumour virus by sera of women with breast cancer.

MOUSE mammary tumour virus (MTV) causes breast cancer in mice. The mouse-MTV system is a useful model in the search for the hypothetical human mammary tumour virus (HMTV) causing the parallel disease in women. B particles similar in morphology to MTV were observed in negatively stained preparations of human milk by Moore et al.1, and there seemed to be a connexion between the appearance of particles in the milk and the incidence of breast cancer among women.

A case of myelocytic leukemia simulating the mouse model diseases.

AbstractA case of myeloid leukemia is reported that occurred in a woman whose previous experiences are known to increase the incidence of myeloid leukemia in the mouse. Ovariectomy and sterile turpentine abscess formation increase the incidence of myeloid leukemia in mice exposed to ionizing radiation. In addition, antigenic similarities exist between certain variants of murine leukemia virus and mammary tumor virus. This patient experienced ovariectomy, thigh abscess formation, and partial body irradiation for carcinoma of the breast a few years before she developed leukemia. An association between human breast cancer and myelocytic leukemia has been described. While this case certainly does not prove that similar pathogenetic mechanisms of myeloid leukemia occur in mice and man, the events preceding the development of leukemia in this patient certainly mimicked the mouse models well.

The Growth Accelerating Effect of Bittner Virus in Monolayers of Baby Mouse Kidney Cells

Murine mammary tumour virus (Bittner virus) is generally detected and titrated by in vivo tests. The time required for these tests varies from about 4 months to more than 1 year according to the clinical criteria accepted (Nandi, 1963). Recently Charney, Pullinger & Moore (1968) reduced this time to about 3 months by inoculation of newborn female mice and the detection of Bittner virus antigens in the milk of young adults by immunodiffusion tests. The immunological technique alone does not discriminate between infective and non-infective Bittner virus antigens. A faster in vitro assay would speed up the research of many aspects of the virus, including those at the cellular and molecular levels. Biological effects of Bittner virus preparations in vitro have been described, but an in vitro assay does not yet exist.