Biomedical subjects
Publications and source records attributed to J R Stephenson.
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Type C RNA viruses can be induced by certain chemicals from cells of many mouse strains. Both C58 and BALB/c cells have been shown to contain endogenous viruses that are designated N-tropic because they grow preferentially in cells of NIH Swiss mouse origin. While demonstrating many similar biological and immunological properties, the C58-induced virus is around 10-fold more infectious per physical particle than the N-tropic virus of BALB/c cells. In the present studies, inoculation of these viruses into newborn NIH Swiss mice led to the development of diseases associated with splenomegaly and lymphadenopathy at similar frequency in each group. The disease induced by C58-MuLV was histophathologically diagnosed as lymphoblastic leukemia and was highly malignant following transplantation into newborn mice. The histopathological appearance of spleens from BALB/c virus-affected animals was distinguishable, demonstrating instead myeloid metaplasia or myelogenous leukemia. These findings provide evidence that different endogenous mouse type C viruses can induce distinct diseases in the same mouse strain. Furthermore, they implicate the N-tropic virus endogenous to C58 cells as a major factor in the development of lymphoblastic leukemia that occurs at high frequency in that strain.
The 70,000 molecular weight glycoprotein (gp70) of a type-C RNA virus originally isolated from a woolly monkey has been partially purified and immunologically characterized. Evidence that this viral protein is viral coded was derived from studies showing its antigenic properties to be unaltered by virus passage in cells of different species. A broadly reactive competition immunoassay was developed utilizing antiserum prepared against feline leukemia virus to precipitate 125I-labeled woolly monkey virus gp70. Gibbon and woolly viruses, as well as feline and several mouse type-C viruses, all reacted with equal efficiency in this assay. In contrast, an endogenous virus of the baboon failed to cross-react, suggesting that viruses of this latter group are less immunologically related to the others. In a homologous competition immunoassay for the woolly viral glycoprotein, the woolly virus was readily distingusihed from otherwise colsely related viruses of gibbon apes. These findings demonstrate the pronounced type-specific antigenic dterminants possessed by this viral protein. The antigenic determinants of gp70 responsible for neutralization have also been investigated.
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Antigens which immunologically cross-react with two mouse C-type viral polypeptides, p30 and p12, are present at very low levels in normal virus-negative mouse cells. These two antigens have been purified by 50-300-fold from cell extracts and shown to cochromatograph with the corresponding labeled viral polypeptides in several systems. Their type-specific antigenicities are shown to be distinct from those of previously tested MuLV isolates suggesting that they may be components of a new class of endogenous C-type virus. The methods utilized in the present studies for concentration of virus-specific antigens of normal mouse cells provide an approach for detection of C-type viral antigens in cells of other species.
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There is increasing evidence that mouse cells of different strains contain different numbers and biologic classes of naturally-integrated type-C RNA viruses. The present studies have examined the cellular regulation of one class of virus, xenotropic in host range, which is common to mice of NIH Swiss and NZB strains. This virus is spontaneously released at high level by NZB embryo cells but its production by NIH Swiss embryo cells is below detectable levels. Quantitative analysis of the chronic level of virus release by embryo cell lines established in tissue culture from genetic crosses of NIH and NZB strains has demonstrated the existence of a partially dominant gene influencing virus release. Evidence is presented indicating that this gene may act to provide a factor necessary for expression of a specific class of endogenous virus.
Mouse cells contain several biologically distinguishable endogenous type-C viruses. In the present studies, the immunologic response of different strains of mice to the natural expression of these viruses has been examined. High titers of neutralizing antibodies have been detected to a class of virus that lacks the ability to exogenously infect mouse cells. The expression of this virus, in vivo as well as in vitro, is shown to be vertically transmitted as a dominant genetic trait. The findings indicate the widespread occurrence of this endogenous virus and the ability of the mouse to immunologically respond to a class of type-C virus whose mode of transmission is similar to that of cellular genes.
In vitro, clonal BALB/3T3 mouse cells were transformed into nonproductive sarcoma cells by Kirsten murine sarcoma virus. The resulting cells are called K-BALB. Similarly, the Kirsten sarcoma virus and woolly monkey sarcoma virus transformed normal rat embryonic kidney (NRK) cells to nonproductive sarcoma cells K-NRK and W-NRK, respectively. The presence of sarcoma cell surface antigen (SCSA) on these three different cell lines has been examined by immunoelectron microscopy using the rabbit anti-K-BALB, anti-K-NRK, and anti-W-NRK sera preabsorbed with normal embryonic rat cells, NRK cells, and BALB/3T3 cells. Four different specific sarcoma cell surface antigens have been demonstrated: SCSAa, an antigen specific to the surface of W-NRK cells; SCSAb, a surface antigen common to K-NRK and W-NRK cells; SCSAc, a surface antigen common to K-BALB and W-NRK cells; and SCSAd, a surface antigen broadly reactive with the rabbit antisera to W-NRK, K-NRK, and K-BALB.
RNA C-type viruses are known to exist in an unexpressed form in all mouse cells. These endogenous viruses can be activated from cells in tissue culture under certain experimental conditions. The biologic activity in vivo of one class of chemically-activated C-type virus has been studied. This virus is shown to induce a specific tumor, lymphatic leukemia, in mice of a low leukemic incidence strain.