Antiviral effect of interferon in vivo may be mediated by the host (original) (raw)

Prevention of Vaccinia Lesions in Rhesus Monkeys by Human Leucocyte and Fibroblast Interferon

Journal of General Virology, 1980

The prophylactic antiviral activity of systemically administered human interferon preparations was tested in 36 rhesus monkeys against vaccinia virus injected into the skin. All nine control monkeys developed typical vaccinia skin lesions. Eight of nine monkeys treated with daily intramuscular injections of leucocyte interferon (5 x io ~ units/kg) from day-I to day + 7 after vaccination were completely protected. No lesions developed after discontinuation of therapy, Administration of the same amounts of leucocyte interferon intravenously (i.v.) was equally effective. Daily intramuscular (i.m.) injections of lower doses of leucocyte interferon (1"2 5 X 105 units/kg; 0"5 × 105 units/kg) decreased the severity of the skin lesions. Lesion scores correlated inversely with the dose of interferon. Four of six animals receiving daily i.m. injections of fibroblast interferon (5 x I05 units/kg) and one of three animals treated i.v. with the same dose were protected against vaccinia virus, and the lesions in the other monkeys were smaller. Intramuscular injections of 5 x 10 5 units/kg of fibroblast interferon or 1-2 5 x I0 5 units/kg of leucocyte interferon resulted in comparable serum levels and had comparable efficacy in reducing lesion scores.

Studies on the Mechanism of Interferon Action

The Journal of General Physiology, 1970

Interferon does not inactivate viruses or viral RNA. Virus growth is inhibited in interferon-treated cells, but apart from conferring resistance to virus growth, no other effect of interferon on cells has been definitely shown to take place. Interferon binds to cells even in the cold, but a period of incubation at 37°C is required for development of antiviral activity. Cytoplasmic uptake of interferon has not been unequivocally demonstrated. Studies with antimetabolites indicate that the antiviral action of interferon requires host RNA and protein synthesis. Experiments with 2-mercapto-1(ß-4-pyridethyl) benzimidazole (MPB) suggest that an additional step is required between the binding and the synthesis of macromolecules. Interferon does not affect the adsorption, penetration, or uncoating of RNA or DNA viruses, but viral RNA synthesis is inhibited in cells infected with RNA viruses. The main action of interferon appears to be the inhibition of the translation of virus genetic infor...

In vivo immune stimulation by interferon during viral infection

Antiviral Research, 1981

Treatment of Rhesus monkeys with human leukocyte interferon prevents the development of skin lesions after intradermal infection with vaccinia virus. The treatment does not prevent the development of immunity to vaccinia. Inactivated vaccinia virus, which is non-immunogenic in untreated monkeys, induced immunity under interferon treatment, indicating that interferon had an immunestimulating effect.

Antiviral activity of human leucocyte interferon in rhesus monkeys and marmosets

Antiviral Research, 1981

When applied before infection human leucocyte interferon (HLI) had a pronounced antiviral activity in vaccinia virus-infected rhesus monkeys. Even one single injection of 500,000 units/kg given before infection yielded significant protection. However, when HLI was applied after infection no significant protection was obtained. In marmosets HLI showed relatively poor antiviral activity. rhesus monkey interferon marmoset vaccinia virus

Interferon treatment inhibits early events in vaccinia virus gene expression in infected mice

Virology, 1991

We have analyzed the role of exogenous administration of mouse interferon (IFNa + 8) on the replication of vaccinia virus in peritoneal cells and in the spleen of Balb/c mice. Mice were pretreated for 10 hr with IFN and then infected with a vaccinia virus recombinant expressing luciferase under an early or late virus promoter, and the enzyme activity was measured in the course of virus infection. A dose of IFN as low as lo3 units/mouse abolished the appearance of luciferase activity in cells of the peritoneal cavity and in spleen cells. The IFN-mediated inhibition of luciferase activity was observed even when mice were infected 4 days after the administration of IFN. The IFN-treated animals were considered free of virus since neither luciferase nor viral proteins were detected in target cells several days after virus infection. Despite a severe IFN-mediated inhibition of luciferase activity, the appearance of luciferase on mRNA levels was not inhibited 6 hr after virus infection. Our finding revealed that replication of vaccinia virus in Balblc mice is exquisitively sensitive to inhibition by IFN and that this effect occurs at early times postinfection, most likely as a result of a translational block. 0 i 991 Academic Press. I~C.

Differentiation of the immunosuppressive and antiviral effects of interferon

Cellular Immunology, 1978

Virus-induced (virus-type) interferon suppression of the in vitro antibody response of mouse (C57B1/6) spleen cells to sheep red blood cells was blocked by 5 X 10d M Z-mercaptoethanol (2-ME). The blockade was not due to a direct effect on interferon since 2-ME was capable of blocking the suppression when added to cultures up to 48 hr after interferon. ZME blockade of virus-type interferon immunosuppression was not due to the immunoenhancing property of 2-ME. Similar protective effects of 2-ME were observed during immunosuppression by virus-type interferon inducers, but not T-cell mitogen inducers of interferon (immune interferon). The data suggest that the immunosuppressive properties of virus-type and immune interferon preparations involve different mechanisms. Virus-type interferon inhibited DNA synthesis in unstimulated spleen cell cultures and in 2-ME stimulated cultures, and the degree of inhibition of DNA synthesis appeared to be related to the immunosuppressive property of interferon in the absence or presence of 2-ME. 2-ME did not affect the antiviral properties of either virus-type or immune interferon in nonlymphoid cells. Further, the induction of virustype interferon in spleen cells was neither inhibited nor enhanced by 2-ME, while the induction of immune interferon was enhanced. This enhancement is consistent with Z-ME enhancement of the immunosuppressive effects of immune interferon inducers. There are two possibilities for 2-ME blockade of the immunosuppressive effect of virus-type interferon, while not affecting the antiviral property. Firstly, the immunosuppressive and antiviral properties of virus-type interferon may involve different mechanisms at the subcellular level. Secondly, the selectivity of the blockade by 2-ME could be due to the fact that spleen cells are the target cells in immunosuppression, while L cells are the target cells in inhibition of virus replication. Thus, virus-type interferon may suppress the immune response at the level of the macrophage and 2-ME may reverse this effect by replacing a blocked macrophage function.

Antiviral Action of Mouse Interferon in Heterologous Cells1

Journal of Bacteriology, 1966

Buckler, Charles E. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), and Samuel Baron . Antiviral action of mouse interferon in heterologous cells. J. Bacteriol. 91: 231–235. 1966.—The antiviral action of mouse interferon in cell cultures of mouse, hamster, rat, chicken, and monkey origin was investigated. Using a vesicular stomatitis virus (VSV) plaque reduction test, we found that mouse serum interferon, assayed on closely related rat or hamster cells, exerted 5% of its homologous antiviral activity. This activity was characterized as interferon by its temperature of inactivation, trypsin sensitivity, nonsedimentability, stability at p H 2, lack of inactivation by antibody to virus, and inability to be washed off cells. In the more distantly related chicken and monkey cells, mouse interferon had less than 0.1% of its homologous activity. Conflicting reports of heterologous activity of chicken and mouse interferon preparations may result in part from the obse...