Biomedical subjects

P Staeheli

Publications and source records attributed to P Staeheli.

98 records · Page 6Linked to original sources

PubMed1985

Interferon-induced protein Mx accumulates in nuclei of mouse cells expressing resistance to influenza viruses.

In mouse cells carrying the dominant influenza resistance allele Mx+ (but not in Mx- cells) interferon-alpha/beta (IFN) induces an efficient antiviral state against influenza viruses and, concomitantly, the synthesis of a 75,000-Da protein (protein Mx). Here, indirect immunofluorescence using monoclonal antibodies was used to demonstrate that protein Mx accumulates in the nucleus of IFN-treated Mx+ cells, suggesting a nuclear site of action. Protein Mx is present in the nucleus of untreated influenza virus-resistant macrophages freshly explanted from the peritoneal cavity of Mx+ mice but is lost with time in culture when peritoneal macrophages become permissive for influenza virus.

Alleles↗

PubMed1985

Interferon-induced guanylate-binding proteins: mapping of the murine Gbp-1 locus to chromosome 3.

GBP-1 is the predominant species of a family of guanylate-binding proteins synthesized in mouse cells in response to interferons (IFNs) alpha, beta, or gamma. IFN inducibility of this 65,000-Da protein is controlled by alleles at a single autosomal locus, Gbp-1, with allele a encoding inducibility and allele b noninducibility. Here, we present evidence suggesting that both alleles occur in outbred populations of wild mice. Using recombinant inbred strains and classical linkage analysis of offspring of two-point and three-point backcrosses we demonstrate that Gbp-1 is linked to Adh-3 (encoding alcohol dehydrogenase C2) and VaJ (varitintwaddler-Jackson) located on the distal part of chromosome 3. The relevant recombination frequencies (RFs) (+/- SE) were 3.5 (+/- 1.1) and 11.7 (+/- 2.8)%, respectively. We further show that strain B6.C-H-23c/By(HW 53), congenic for a small segment of chromosome 3, carries the BALB/c alleles at both the Gbp-1 and the Adh-3 locus and not the alleles of the B6 background strain confirming the chromosomal location and close linkage of the two loci.

Animals↗

PubMed1985

Interferon-induced human protein with homology to protein Mx of influenza virus-resistant mice.

Polyclonal and monoclonal antibodies with specificity for protein Mx (a karyophilic 75,000-dalton protein induced by interferon [IFN] in mouse cells carrying the influenza virus resistance allele Mx+) detected an IFN-induced 80,000-dalton protein in peripheral blood lymphocytes and in fibroblasts of healthy human donors. The human protein, like protein Mx, was induced by IFN-alpha but not by IFN-gamma. Unlike the mouse protein, it was predominantly localized in the cell cytoplasm.

Alleles↗

PubMed1984

Mx-dependent resistance to influenza viruses is induced by mouse interferons alpha and beta but not gamma.

In cells derived from congenic BALB.A2G-Mx mice carrying the resistance gene Mx, but not in cells from BALB/c mice lacking Mx, mouse interferons alpha and beta induced the synthesis of a unique cellular protein that was associated with an efficient antiviral state with selectivity for influenza viruses. In contrast, native or recombinant mouse interferon gamma failed to efficiently protect Mx-bearing cells against influenza viruses and did not noticeably induce the synthesis of the Mx-associated protein, although interferon gamma was as effective as interferons alpha and beta in protecting BALB.A2G-Mx and BALB/c cells against the rhabdovirus VSV. These results demonstrate that different types of interferons differentially regulate the expression of the Mx gene and thereby induce distinct antiviral states.

Animals↗

PubMed1984

Genetic control of interferon action: mouse strain distribution and inheritance of an induced protein with guanylate-binding property.

Interferons (IFNs) induce in responsive cells the synthesis of various proteins including a set with high binding affinities to guanylates. These guanylate-binding proteins (GBPs) were analyzed in cells from 46 inbred mouse strains using GMP-agarose affinity chromatography. In cells of 11 strains, including A/J, BALB/cJ, and C3H/HeJ, type I and II IFNs induced the synthesis of a major GBP of Mr 65,000, designated here GBP-1, and of at least three minor GBPs. In contrast, cells of the remaining 35 strains, including DBA/2J, C57BL/6J, and A2G, failed to synthesize GBP-1 in response to both types of IFNs. Induction of the minor GBPs was comparable in cells of both groups of mice, confirming that they were all responsive to IFNs. Analysis of F1, F2, and BC1 offspring of crosses between GBP-1 inducible (A/J) and noninducible (DBA/2J or A2G) strains showed that inducibility of GBP-1 was inherited as a single autosomal gene. The symbol Gbp-1 is proposed for this locus, designated Gbp-1a for the allele causing inducibility and Gbp-1b for the other allele.

Alleles↗

PubMed1983

Expression of interferon dependent resistance to influenza virus in mouse embryo cells.

Adult but not newborn mice bearing the allele M chi display a specific resistance to in vivo infection with orthomyxoviruses. In vitro, cells isolated from adult M chi-animals exhibit a several hundred-fold higher sensitivity to the action of interferon (IFN) against influenza viruses than do cells from M chi-negative mice. We here tested whether or not cells from immature M chi-bearing animals would likewise express the virus-specific higher sensitivity to IFN. Cultured cells from 16-day gestation mouse embryos with and without M chi were equally permissive for an influenza virus when single cycle virus growth was measured. However, influenza virus plaques were smaller in M chi-cells. Treatment of cells with mouse interferon reduced viral protein synthesis, single cycle virus yields and the number of virus plaques more efficiently in M chi-cells than in non-M chi-cells. The smaller size of influenza virus plaques in M chi-cells not treated with IFN seems to be due to the action of endogenous IFN:inclusion of anti-interferon antibodies in the agar overlay during plaque formation resulted in plaques of approximately the size seen in control cells. When treated with the same dose of IFN, cells with M chi developed protection against influenza virus more rapidly than cells without M chi. However, after removal of IFN, the antiviral protection decayed more rapidly in cells in cells without M chi. No differences in sensitivity to IFN, viral plaque formation and kinetics of induction and decay of the antiviral state were observed between the two cell types when the rhabdovirus VSV was used as challenge. Thus, the allele M chi is expressed in cultured embryo cells much as in cells from adult animals, and susceptibility of newborn M chi-animals to influenza virus infection cannot be due to inability of their cells to respond to IFN appropriately.

Alleles↗

PubMed1983

Interferon induces a unique protein in mouse cells bearing a gene for resistance to influenza virus.

Mouse cells carrying the dominant resistance gene Mx develop a more efficient antiviral state toward influenza viruses in response to interferon than do Mx-negative cells. We have identified an Mx gene-associated product by labeling cultured peritoneal macrophages and embryonic cells with [35S]methionine in the presence or absence of interferon. The radioactive proteins from unfractionated cytoplasmic extracts were separated electrophoretically in two dimensions and were revealed by fluorography. A protein with a Mr of 72,500 and an isoelectric point of 6.3 was induced by mouse interferon type I (a mixture of alpha and beta interferons) in cells carrying the gene Mx but not in cells lacking Mx. The induction of this protein could be blocked by actinomycin D. The maximal rate of synthesis was reached in embryonic cells 4-5 hr after treatment with 10(3) reference units of interferon per ml. When the allele Mx (present in the inbred mouse strain A2G) was repeatedly backcrossed on different genetic backgrounds (BALB/c, C57BL/6, A/J), a clear correlation between the inducibility by interferon of this protein and the presence of the allele Mx was observed. The results suggest that this protein induced by the interaction of interferon with Mx plays a role in the selective antiviral state against influenza viruses that is observed in interferon-treated Mx-bearing cells.

Animals↗

PubMed1983

Different mRNAs induced by interferon in cells from inbred mouse strains A/J and A2G.

Treatment of cells from inbred mouse strains A/J and A2G with interferon resulted in the development of different antiviral states for influenza viruses. A2G mice-derived cells that carry the resistance gene Mx were efficiently protected by interferon against influenza viruses, whereas the interferon protection against the same viruses in wild-type A/J mice-derived cells was only marginal. The two cell types, however, were equally protected by interferon against vesicular stomatitis virus and other non-orthomyxoviruses. The interferon-induced mRNAs of mouse embryonic fibroblast cells that carried either homozygous wild-type alleles or homozygous Mx alleles were compared. The isolated polysome-bound mRNAs from A/J (+/+) and A2G (Mx/Mx) cells were translated in a cell-free translation system, and the translation products were analyzed after two-dimensional gel electrophoresis. New mRNAs coding for at least eight proteins with molecular weights (MW) ranging from 30,000 to 80,000 were found in interferon-treated cells but not in control cells. Differences in the interferon-induced mRNAs from A/J and A2G cells were also found. An mRNA coding for a 72,000-MW protein was found in interferon-treated A2G cells but not in interferon-treated A/J cells. Interferon-treated A/J cells, on the other hand, contained an mRNA coding for a 65,000-MW protein that was not found in interferon-treated A2G cells. The in vitro-synthesized 65,000-MW protein efficiently bound to GMP. Cytoplasmic extracts prepared from interferon-treated A/J cells also contained a GMP-binding 65,000-MW protein that was undetectable in similarly treated A2G cells.

Animals↗