The Interferon System in Man: Nature of the Interferon Molecules and Mode of Action

Revel, Michel

doi:10.1007/978-1-4613-3804-8_21

Cited by 21 publications

(12 citation statements)

References 449 publications

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“…These two groups of structurally dissimilar molecules with their own unique receptors exhibit antiviral, antimitogenic, immunoregulatory, and cellular differentiation activities (44)(45)(46). Two-dimensional electrophoresis of polypeptides derived from IFN-a/3-or IFN-y-treated cells (47) The observed chromosome 21 dose-dependent sensitivity for both Hu-IFN-a and Hu-IFN-y activity (48) also suggests a common transduction pathway.…”

Section: Resultsmentioning

confidence: 99%

Human chromosomes 6 and 21 are required for sensitivity to human interferon gamma.

Jung¹,

Rashidbaigi²,

Jones³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

129

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The human interferon y receptor has previously been assigned to chromosome 6. Chromosome 6 also encodes HLA, the human class I major histocompatibility antigens. However, the presence of chromosome 6 in hamster-human hybrids is by itself insufficient to confer sensitivity to human immune interferon as measured by the induction of human HLA. Human chromosome 21 was found to be the second chromosome essential for HLA inducibility.Similar results were found with mouse-human somatic cell hybrids. Thus, at least two steps are involved in the action of human interferon y: the binding of interferon Yto its receptor coded by chromosome 6 and the linkage of this binding event through a factor coded by chromosome 21 to trigger biological action. Both of these steps are species-specific.The antiviral action of interferon y (IFN-y) is overshadowed by its ability to mediate a multitude ofother biological effects. IFN-y, by itself or synergizing with lymphotoxins, has much greater cytostatic and cytotoxic effects than IFN-a//3 (1-3).The major histocompatability complex (MHC) antigens are greatly enhanced with IFN-y: the class I human HLA-A, B, C and f-microglobulin (4-6), or the mouse H-2 antigens (7), the class II human HLA-DR, -SB and -DC (8-10), or the mouse Ia antigens (11), and the class III complement and factor B antigens expressed by mononuclear phagocytes (12). Other immunoregulatory effects of IFN-y include its ability to potentiate macrophage cytotoxicity or phagocytosis, possibly through the stimulation of IgG Fc fragment receptors (13-15). IFN-y can also induce the differentiation of myeloid cells into the monocytic pathway (16). The pleiotropic response to IFN-y suggests complex interactions beyond the ligand-receptor binding.We previously reported the localization of the human interferon y (Hu-IFN-y) receptor to chromosome 6 (17-19). Here we report a genetic approach that has begun to unravel this complex system of signal transduction. Initial experiments had indicated that chromosome 6, unlike chromosome 21 and its Hu-IFN-tx// receptor (20), is by itself incapable of conferring biological sensitivity to Hu-IFN-y. The long and short arms of chromosome 6 encode the Hu-IFN-y receptor (17) and the HLA antigens (21), respectively. The presence of human chromosome 6 in a heterologous host, therefore, provides a convenient system to determine whether other chromosomes are necessary to modulate the expression of MHC antigens. Through the use of somatic cell hybrids we have delineated the human chromosomes essential for induction of class I MHC antigens by Hu-IFN-y. EXPERIMENTAL PROCEDURES IFNs, Radiolabeling and Covalent Crosslinking. Recombinant Hu-IFN-aA/D(Bgl) and Hu-IFN-y, with respective specific activities of 1.9 x 108 units/mg and 1 x 107 units/mg were purified from Escherichia coli as described (22-24) by R. Ning, S. J. Tarnowski, C. J. Chen, F. Khan, and J. Langer. Mouse interferon y (Mu-IFN-y) with a specific activity of about 1 x 107 units/mg was a gift from M. Sheppard of Genentech. Antiviral titer...

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Section: Resultsmentioning

confidence: 99%

Human chromosomes 6 and 21 are required for sensitivity to human interferon gamma.

Jung¹,

Rashidbaigi²,

Jones³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

129

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“…Thestrup-Pederson and co-workers'6' reported the appearance of a break or gap in the long arm of one of the chromosomes in pair 16 (designated 16q22) in 20% of the lymphocytes of a patient being treated with a-IFN because of an Epstein-Barr virus-induced lymphoproliferative disorder. This defect was apparently not disease associated because it was also observed in approximately 50% of the mother's lymphocytes after treatment in vitro with IFN at 2-5,000 U/ml.…”

Section: Introductionmentioning

confidence: 99%

Chromosomal Aberrations in Muntjac Cells Resulting From Exposure to Interferon

Jasny¹,

Tamm²

1985

Journal of Interferon Research

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Cells of the Indian deer (Muntiacus muntjac) are sensitive to the antiviral and antiproliferative action of human beta-interferon (beta-IFN). Because of their low diploid chromosome number and readily identifiable chromosomes, they provide a convenient model system in which to test for the ability of IFN treatment to result in chromosome abnormalities. Increases in the frequencies of chromosome gaps and breaks have been observed after 72 h of treatment with IFN at a concentration of 100 U/ml. At IFN concentrations of 10-100 U/ml, there is a higher proportion of aberrations in the X chromosome than would be expected in a random distribution. At 1,000-1,700 U/ml IFN, there is an increase in the proportion of cells with multiple abnormalities over that observed at 0-100 U/ml IFN, and the distribution of aberrations appears to be random.

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“…2'-5'-Oligo(A)-dependent endonuclease is a key enzyme in the classic IFN response (Silverman et al, 1982;Revel, 1984;Whitaker-Dowling & Youngner, 1987). Is-1 was found to induce a consistently greater level of rRNA cleavage than is + in protected cell lines (Fig.…”

Section: Discussionmentioning

confidence: 99%

Selection and Characterization of Interferon Response Mutants from Mouse L929 Fibroblast Cells

Sakuragi

Simon²

1988

Journal of General Virology

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SUMMARYInterferon (IFN) response mutants were selected from mouse L929 fibroblast cells and their specific resistance to is-I, an IFN-sensitive mutant of mengovirus, was studied. The standard L cell subline used in our laboratory (G3), is resistant to is-1 infection after pretreatment with low levels of IFN. Two clonal sublines that support the growth of is-1 in the presence of IFN (AS-4 and TA-6) were isolated from it, and two revertant lines (AS-4R1 and TA-6R1) were subsequently selected from AS-4 and TA-6. The kinetics of is-1 growth in the presence of IFN were found to vary in each of these sublines. Specific resistance to is

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The Interferon System in Man: Nature of the Interferon Molecules and Mode of Action

Cited by 21 publications

References 449 publications

Human chromosomes 6 and 21 are required for sensitivity to human interferon gamma.

Human chromosomes 6 and 21 are required for sensitivity to human interferon gamma.

Chromosomal Aberrations in Muntjac Cells Resulting From Exposure to Interferon

Selection and Characterization of Interferon Response Mutants from Mouse L929 Fibroblast Cells

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