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.
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...
An immunoenzyme quantitative assay for the antiviral effect of interferons
Journal of Immunological Methods, 1984
A technique is described for measurement of the antiviral activity of interferon by an immunoenzymatic assay for viral proteins. Cells treated by tested samples of interferon (IFN) are infected with vesicular stomatitis virus (VSV) and following the development of viral cytopathy are lysed by the addition of deoxycholate and then transferred into ELISA microplates. The viral proteins bind effectively to the microplates proportionally to their level in the culture and may be measured by incubating the plates sequentially with (1) rabbit antiserum against VSV, (2) a conjugate of alkaline phosphatase either to protein A or to an antibody against rabbit lgG and (3) p-nitrophenylphosphate. This procedure may be further simplified by using antibodies against VSV to which alkaline phosphatase has been directly conjugated. We found this immunoenzyme assay to be superior to the 'cytopathic effect inhibition' assay in precision and sensitivity and in being independent of the effectiveness of viral cytopathy.
Journal of General Virology, 1983
A simple solid-phase immunoassay for quantification of vesicular stomatitis virus (VSV) is described. Infected cultures are lysed with deoxycholate. Samples of the lysates are transferred to PVC immunoassay plates and the amount of virus protein adsorbed to the plates is then quantified by sequential incubation with antiserum against VSV proteins and 125I-labeUed Protein A. The decrease of VSV protein in interferon (IFN)-treated cultures is correlated with inhibition of formation of infectious virions; its quantification therefore allows accurate measurement of the antiviral effect. The applicability of the immunoassay for measuring the virus yield is not restricted to cells exhibiting a virus cytopathic effect. Moreover, since the decrease of virus protein is obtained at IFN concentrations lower than those that reduce cell killing by the virus, the assay provides a more sensitive measure for the IFN effect than that obtained by 'cytopathic effect inhibition' assays.
Journal of General Virology, 1981
Five human interferon-a (leukocyte) subtypes derived from genes cloned in Escherichia coil have been compared for their ability to induce antiviral activity against vesicular stomatitis virus infection of various mammalian cell cultures. These interferons, designated LeIF-A (IFN-ct2) , -B, -C, -D (IFN-a~) and LeIF-F, show different relative activities when assayed on human; bovine, hamster, mouse, rabbit and monkey cell lines. As with a natural human buffy-coat interferon-a preparation, three subtypes (LeIF-B, -C and -D) showed considerable activity on RK-13 rabbit cells, but two (LeIF-D and -F) also showed some activity on mouse L-929 cells. Of the five interferon subtypes examined, LeIF-F demonstrated the highest degree of species specificity.
Journal of interferon research, 1982
The induction of protein phosphorylation and the inhibition of virus replication by several subspecies of human alpha (leukocyte) interferon (HuIFN-a) were examined in human and monkey cells in culture. Five recombinant IFN-a subspecies synthesized in Escherichia coli, IFN-aB, aC, aF, ai, and aS, all inhibited vesicular stomatitis virus (VSV) replication in both human amnion U and monkey kidney BSC-1 cells. The relative specific antiviral activity varied in the order ai > aB =aF > aC = aJ in both human U and monkey BSC-1 cells. By contrast, the double-stranded RNA (dsRNA)-dependent phosphorylation of ribosome-associated protein P, was induced in human U cells but not in monkey BSC-1 cells by IFN-aB, aC, aF, ai, and aJ. Furthermore, two forms of P, phosphorylation were induced in U cells by all five of the IFN-a subspecies: one form was clearly detectable after 2.5 h of IFN treatment, whereas the other phosphorylated form required longer periods of IFN treatment and was superinduced by the addition of actinomycin D following IFN treatment. Using one of the cloned IFN subspecies, ai, the induction of both forms of P, phosphorylation in human U cells was shown to depend upon the concentration of IFN during treatment. However, similar to BSC-1 cells, protein phosphorylation was not induced by IFN-al in human fibroblast GM2767A cells although an antiviral state was induced in GM2767A cells. These results suggest that the ability of individual human IFN-a subspecies to induce protein phosphorylation and inhibit virus replication is specified by the host cell rather than the IFN-a subspecies. This conclusion is further supported by the observation that the human recombinant hybrid IFN-aA/D inhibited both reovirus and vesicular stomatitis virus (VSV) replication in monkey BSC-1 cells, whereas in human U cells reovirus was virtually unaffected by IFN-aA/D even though VSV replication was fully inhibited.
Virology, 1984
In this investigation the sensitivity of vaccinia virus to interferon (IFN) has been examined in cultured cells. In a variety of mouse and human cells of different origins vaccinia virus functions (RNA, protein, and virus yields) were found to be relatively resistant to IFN. In these systems, the levels of the IFN-mediated enzyme activities (2-5A synthetase and protein kinase) were severely impaired by the virus. This virusmediated inhibitory effect developed with time after infection and was dependent on viral protein synthesis. Mixed infections between vaccinia virus and viruses (VSV or polio) which are sensitive to IFN showed that both protein synthesis and virus yields were not inhibited. These findings show that vaccinia virus can overcome the antiviral action of IFN and that viral gene functions appear to be involved in this interference phenomenon.
Formation of Non-infective Herpesvirus Particles in Cultured Cells Treated with Human Interferon
Journal of General Virology, 1984
Treatment of HeLa cells with human lymphoblastoid interferon [HulFN-~(Ly)] induced an antiviral state that rendered the cells refractory to infection by herpes simplex virus type 1 (HSV-1), and the yield of infectious HSV-1 was reduced by 98%. Analysis of the mechanism of the anti-herpes action of IFN indicated that no gross inhibition of viral protein synthesis took place and late proteins appeared, although the synthesis of some of them was partially inhibited. No differences were apparent between the glycoproteins or phosphoproteins synthesized in control and IFN-treated HSV-l-infected HeLa cells. No inhibition of the formation of new virus particles from IFN-treated cells was evident as assessed by electron microscopy and biochemical analyses, although their infectivity was drastically reduced. These virions exhibited some differences in their content of a few proteins as determined by PAGE. Studies on the second infection cycle with virions obtained from IFN-treated cells suggested that they attached and penetrated HeLa cells but that their development was impaired, since no viral protein synthesis was observed during the second infection. Altogether these results do not support the idea that the molecular mechanism of action of human IFN against HSV-1 is mediated via the 2'-5'A system, or by the inactivation of initiation factors. Rather, they focus the problem of the anti-herpes action of IFN at the level of formation of defective virions.
Proceedings of the National Academy of Sciences, 1980
Treatment of human fibroblast FS-4 cultures with human type II interferon preparations induced the synthesis of at least four proteins that were similar in size to four of the five proteins induced by type I interferons (Mr 120,000, 88,000, 67,000, and 56,000). However, the Mr 67,000 and 56,000 proteins were induced more strongly by type II than by type I interferon, and a counterpart of a Mr 80,000 protein induced by type I interferons was not noticeably induced by type II interferon preparations. We therefore compared type I and type II interferons for relative antiviral activities against different viruses (vesicular stomatitis, encephalomyocarditis, and vaccinia viruses and reovirus) and for cell growth-inhibitory activities on various cell types. The replication of vesicular stomatitis and encephalomyocarditis viruses was inhibited more strongly by type I interferon, whereas reovirus and vaccinia virus showed greater sensitivity to type II interferon preparations. This indicate...
Fate of interferon-treated cells
Infection and Immunity, 1976
Interferon-treated cultures of Ly cells survived initial infection with high mul- tiplicities of vesicular stomatitis (VSV) or herpes simplex virus (HSV). In the case of HSV, infectious virus and intracellular viral antigen were rapidly elimi- nated from the interferon-treated cultures, and the cells grew out to form ap- parently normal monolayers that could be cultured indefinitely. In the VSV- infected L. cultures, virus titers remained at low levels in interferon-treated cells but after about 14 days rapidly rose and the culture was destroyed. If inter- feron was added to the medium on days 4 and 6 after infection, virus titers rapidly declined but again recovered and the cells were destroyed. If, however, interferon treatment was resumed 9 days after initial infection, detectable infec- tious VSV was eliminated from the medium. Several methods, including co- cultivation and molecular hybridization, failed to demonstrate persistence of a significant portion of the VSV genome in these cultures.