Biomedical subjects
Publications and source records attributed to I Gresser.
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The genetically determined resistance towards orthomyxoviruses exhibited by mice homozygous (A2G) or heterozygous (A2G X A/J) for the gene Mx was abolished or greatly diminished by treatment with anti-interferon globulin (AIF). AIF induced increased susceptibility to challenge with hepatotropic, neurotropic, and pneumotropic strains of influenza A virus. Hepatotropic virus titers in blood and livers of AIF-treated, Mx-bearing mice were higher by a factor of 10(3)--10(6) than those in untreated mice of the same genotype, and were comparable to those in genetically susceptible (untreated or AIF-treated) mice. Peritoneal macrophages from Mx-bearing untreated mice were resistant to challenge with a macrophage-adapted strain of influenza A virus even in the presence of AIF. However, when macrophages were taken from resistant mice injected with AIF and also cultivated in the presence of AIF, they were as susceptible to the virus as macrophages taken from susceptible mice. We conclude that interferons is an important factor in resistance to orthomyxoviruses governed by the gene Mx.
Human leukocyte interferon increased the expression of HLA-A, B antigens and beta 2-microglobulin on two lines of human lymphoblastoid cells and on peripheral blood lymphocytes. No effect was observed on the expression of HLA-DR antigens.
We have determined the effect of a single injection of potent sheep anti-mouse interferon globulin on polyoma-virus-induced early runting disease and tumor formation in Swiss mice. When newborn mice were injected with greater than or equal to 9 X 10(6) PFU of polyoma virus, 16% (7/44) of mice runted and died in contrast to 96% (45/47) of mice injected with virus and anti-interferon globulin. Likewise, a greater percentage of mice injected with lower doses of virus and anti-interferon globulin developed tumors than did control virus-injected mice. These results suggest that interferon is an important factor in determining the susceptibility of newborn mice to polyoma virus.
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We have compared the interferon sensitivity of parental 10T1/2 cells, having a phenotype characteristic of normal cells, with that of transformed cells isolated after X-irradiation of treatment with methylcholanthrene. Transformed cells were 10- to 20-fold less sensitive than the parental untransformed cells to the antiviral action of interferon and were also less sensitive to the inhibitory effect of interferon on cell multiplication. The decreased sensitivity of these cells to interferon is a useful marker of the transformed phenotype.
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Electrophoretically pure mouse interferon was examined for a number of biologic effects previously ascribed to crude or partially purified interferon preparations. These effects include: inhibition of the growth of a transplantable tumor in mice; inhibition of cell multiplication of mouse tumor cells in vitro; enhancement of the expression of histocompatibility antigens on mouse tumor cells in vitro; inhibition of antibody formation in vitro; inhibition of sensitization to sheep erythrocytes and the expression of delayed type hypersensitivity in mice; enhancement of natural killer cell activity in vivo and in vitro; enhancement of cell sensitivity to the toxicity of poly(I)-poly(C); and enhanced production ("priming") of interferon production in vitro. Our results establish that the molecules responsible for the antiviral action of interferon are also responsible for these varied biologic effects.
Suckling rats were injected for 14 to 17 days with potent rat-cell-culture interferon preparations or various heterologous interferon or control preparations. Only treatment with rat interferon resulted in a delay in growth and maturation of different organs and the subsequent development of an "immune complex" type nephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis. Thus, 38 of 43 rats treated with rat interferon developed a severe glomerulonephritis, whereas only 3 of 99 rats in the various control groups had minimal renal lesions. Deposits of IgG and C3 along the glomerular basement membrane were only seen in interferon-treated rats.
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Mouse interferon has been purified to homogeneity by twostep affinity chromatography. Two polypeptide bands were obtained on sodium dodecyl sulphate--polyacrylamide gel electrophoresis migrating at molecular weights 35,000 and 22,000, both having antiviral activity. The 35,000 but not the 22,000 band, also stained with periodic acid--Schiff. The specific activity was 8 X 10(9) of our laboratory units, corresponding to 2.4 X 10(9) NIH reference units.
We have determined the effect of sheep anti-mouse interferon globulin on the anti-tumor effects of poly I-C, statolon, tilorone, pyran copolymer and BCG in mice inoculated with Ehrlich ascites or L 1210 lymphoma cells. Whereas the anti-tumor effects of poly I-C and statolon were nulified when mice were injected with immunoglobulins, the anti-tumor effects of pyran copolymer and BCG were not modified by this treatment. We conclude that interferon mediates the anti-tumor activity of poly I-C and statolon in these experimental systems. It is suggested that anti-interferon serum provides a direct method of determining whether other biologic effects attributed to viruses, poly I-C, statolon, tilorone, pyran copolymer (and possibly other interferon inducers) are mediated or not by interferon.
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