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Evidence of circulating interferon-gamma in newly diagnosed diabetic children.

Acid-stable interferons (IFN-alpha or IFN-beta) are produced by nucleated cells infected by virus, while acid-labile interferon (IFN-gamma) is synthesized by activated T-lymphocytes. IFN-gamma or an atypical form of acid-labile IFN-alpha have been observed in the circulation of some patients with autoimmune disease. It is believed that autoimmunity and/or viral infections are involved in the pathogenesis of insulin dependent diabetes mellitus. We therefore examined the sera of newly diagnosed diabetic children for the presence of virus-induced or acid-labile IFN. Significant IFN levels (greater than or equal to 8 U/ml) were observed in 11 of 29 patients when compared to 31 healthy children in the same age range. The inhibitor is characterized by species specificity, acid-lability and neutralization with anti-serum for IFN-gamma.

Antiviral Agents↗

Fetal response to viral infection: interferon production in sheep.

When virus was inoculated intravenously during the third trimester, the gestating ewe produced only low amounts of serum interferon, whereas the fetal lamb had the capacity to produce extremely high amounts. There was no evidence of transplacental transfer of interferon between mother and fetus in either direction.

Animals↗

Human chromosome 21 dosage: effect on the expression of the interferon induced antiviral state.

Human primary skin fibroblasts trisomic for chromosome 13, 18, or 21 and diploid human skin fibroblasts were induced for an antiviral response with human interferon. The cells that were trisomnic for chromosome 21 were three to seven times more sensitive to protection by human interferon than the normal diploid or trisomic 18 or 13 fibroblasts. The differential response in trisomnic 21 cells is consistent with the known assignment of the human antiviral gene to chromosome 21.

Alleles↗

Tunicamycin enhances the antiviral and anticellular activity of interferon.

The inhibitory effects of interferon on virus multiplication and cell growth are significantly enhanced by treatment with tunicamycin. Potentiation of antiviral activity was found only with enveloped viruses and not with nonbudding viruses. Changes in the plasma membrane of treated cells may account for this effect, since enveloped viruses bud from the cell surface as a terminal step.

Animals↗

Treatment of mengovirus infection in mice with statolon.

A single intraperitoneal injection of statolon was shown to exert a therapeutic effect on mice previously injected with the large plaque-forming variant of mengovirus. The ld(50) and survival time data demonstrated that such treatment was effective when given 2 to 48 hr after infection. No protective effect was apparent when statolon was administered 3, 4, or 5 days after the viral challenge. It was concluded that statolon, or other similar interferon inducers, may be of therapeutic value in instances of accidental or other known exposure to hazardous viral agents.

Animals↗

Antiviral activity in tissue culture systems of bis-benzimidazoles, potent inhibitors of rhinoviruses.

(S,S)-1,2-bis(5-methoxy-2-benzimidazolyl)-1,2-ethanediol showed antiviral activity in monolayer tissue culture systems against 55 strains of rhinovirus, three types of poliovirus, and strains of type A and B coxsackieviruses. Neither the compound nor any of the analogues tested showed virucidal activity. Its antiviral activity was not associated with interference with viral attachment to or penetration into the cell. At a concentration of 0.1 mg/ml, this group of compounds was generally nontoxic to WI-38, primary bovine kidney, and African green monkey kidney cells and had antiviral activity with 100% inhibition of virus-induced cytopathic effects (CPE). At antiviral levels, these compounds prevented CPE of up to 10(6) median tissue culture infective dose units of virus and completely inhibited formation of new infective virions. The compounds showed antiviral activity both prophylactically and therapeutically against rhinoviruses. Infected cultures could be cleared of CPE up to 90 hr after infection.

Animals↗

In vitro studies with Modoc virus in Vero cells: plaque assay and kinetics of growth, neutralization, and thermal inactivation.

A sensitive and quantitative assay system is described for plaquing Modoc virus in Vero cells. Neutralizing antibodies to Modoc virus could be detected by using this in vitro system by their interference with viral plaque formation. Virus was readily neutralized within 30 min at 37 C by a 1:10 dilution of hyperimmune hamster serum. The rate of neutralization and the total amount of virus neutralized was not altered significantly by the addition of 20 U of guinea pig complement to the hyperimmune hamster serum. A study of the growth of Modoc virus in Vero cells is also presented. After an initial latent period of 20 h, viral titer increased exponentially for 20 h. By 83 h after infection, 8,000 plaque-forming units of virus were detected per cell. The stability of viral infectivity in phosphate-buffered saline at pH 7.4 was evaluated. No reduction in viral titer was detected after 3 days at 7 or 22 C. A continuous decrease in infectivity at 37 C was observed, however, throughout the observation period.

Animals↗

Performance of a commercial immunoglobulin M antibody capture assay using analyte-specific reagents to screen for interfering factors during a West Nile virus epidemic season in Nebraska.

In 2003, the Nebraska Public Health Laboratory tested more than 10,371 serum and 516 cerebral spinal fluid specimens. Results showed that without performing the interfering factors screen for specimens in the low positive index value range of >1.1 to <or=3.5, a false positivity rate of 6.5% would have been realized.

Antibodies, Viral↗

Interferon induction by poly (I): poly (C) enclosed in phospholipid particles.

Liposomes were prepared with phospholipids (sphingomyelin, lecithin, and phosphatidylethanolamine) in combination with cholesterol and charged lipids (dicetyl phosphate and stearylamine) and contained either poly(I):poly(C) or poly(I). Neutral and positively charged liposomes attached much better to L-929 cells in tissue culture than did negatively charged particles. Liposomes were toxic to L cells at relatively low concentrations, making the determination of antiviral activity induced by particles containing poly(I):poly(C) difficult to measure by the plaque reduction assay. When injected into mice, all of the liposomes containing poly(I):poly(C), except phosphatidylethanolamine liposomes, greatly potentiated and extended the serum interferon response of poly(I):poly(C). Lecithin and sphingomyelin liposomes given intravenously were ten times more effective than free poly(I):poly(C) in stimulating production of serum interferon. Sphingomyelin liposomes containing [(14)C]poly(I):poly(C) were 88% cleared from the bloodstream of mice by 3 min after intravenous injection. Most of the radioactivity (70%) was captured by the liver and remained there for at least 4 h. By 2 h, 7% of the radioactivity could be found in the spleen. Five percent of the radioactivity was found in the lungs at 30 min, with decreasing amounts thereafter. Small amounts of radioactivity were found in the muscle and kidneys. The spleen was shown to contain appreciable levels of interferon at 4 h, and low levels were found in the liver. Radioactivity accumulated slowly in the liver following an intraperitoneal injection of sphingomyelin liposomes containing [(14)C]poly(I):poly(C). By 4 h, 26% of the dose was recovered from the liver and 4.9% from the spleen, with small amounts in the lung, kidney, and omentum.

Animals↗