Antiviral Effect Of Interferon Research Articles

Antiviral effect of interferon on influenza virus infection in mice.

The antiviral effect of highly purified mouse interferon (IFN) was studied on influenza virus infection in mice, by changing the routes of administration. By repeated intravenous (i.v.) administrations of IFN, no antiviral effect was observed. However, IFN was effective when the infected mice received either intraperitoneal (i.p.) or intranasal (i.n.) administrations. While all of the untreated mice died within 10 days after infection, 20% of the i.p. treated mice and 67% of the i.n. treated mice survived more than 30 days. To explain these different effects after administration by different routes, the distribution of given IFN in mouse organs was examined. Fifteen min after i.v. injection, only a low-titered IFN was detected in the serum, lung, spleen and liver of the mice and soon disappeared. However, a relatively high-titered IFN was detected 30 min after i.p. administration in the lung and serum. After i.n. administration, high-titered IFN was detected in the lung within 15 min after administration and continued for 90 min. Thus the findings demonstrated that the maintenance of a detectable amount of IFN in mice organs is dependent on the route of administration, and the higher the titer of IFN in the lung, the higher the protective effect of IFN against influenza virus infection.

Interferon-specific effects on protein synthesis in P3HR-1 cells.

The effect of interferon (IFN) on protein synthesis was studied in the Burkitt's lymphoma cell line P3HR-1 by [35S]methionine labelling of the cells, followed by two-dimensional gel electrophoresis of cell extracts. De novo synthesis of three proteins (mol. wts. 33 000, 62 000, and 98 000, respectively) and alterations in the rate of synthesis for a small number of additional proteins were observed during the first 12 h of treatment, while the rate of overall protein synthesis was unaffected. Treatment of P3HR-1 cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or hydrocortisone (HC), which induce similar changes in cell cycle distribution as does IFN, did not induce comparable changes in the rates of protein synthesis. Thus, the effects were specific for IFN and not induced by the change in cell cycle distribution per se, i.e., accumulation in G0. Treatment of cells with 2'-5' pA core did not mimic the effect of IFN at the translational level. A substrain of P3HR-1 cells, selected for resistance to the anti-proliferative effect of IFN, lacked six proteins found in the wild-type. The 62 000 mol. wt. protein was induced in this substrain as well as in native P3HR-1 cells on addition of IFN. The resistant substrain still developed an anti-viral effect in response to IFN. Thus, it seems as if the anti-proliferative and anti-viral effects of IFN, at least in some cells are mediated by different intracellular molecular mechanisms.

Analysis of antiviral state in RD114 and A204 cells after interferon treatment.

Interferon exerts antiviral and various non-antiviral activities on cells. For the development of the antiviral state in cells against exogenous infection of cytolytic viruses such as vesicular stomatitis virus and encephalomyocarditis virus (EMCV), induction of 2'-5'-oligo(A) synthetase or double-stranded (ds)-RNA-dependent protein kinase, or both, has been shown to have a crucial role (Revel 1979). However, in some cases, the antiviral effects of interferon are virus-specific (Nilsen et al. 1980; Samuel & Knutson 1981). Recently, different effects of mouse interferon on retrovirus production and on EM CV replication in a clonal cell line from NIH / 3T3 cells were reported (Gzarniecki et al. 1981).

Interferon Interactions with Thyroid Cells

Iodide uptake by functioning rat thyroid (FRTL) cells is increased by mouse interferon. The effect is detectable using purified interferon; it is not accompanied by an increase in intracellular cyclic AMP levels, is measurable within 20 min, and is prevented by cholera toxin, an agent which inhibits interferon's antiviral activity. The effect of interferon is biphasic with maximally increased iodide uptake (approximately 2-fold) evident at about 300 international mouse units per ml (U/ml) and lesser effects evident at higher concentrations (greater than 1000 U/ml). The effect of mouse interferon on iodide uptake is accompanied by an extremely sensitive antiviral response. Thus, significant antiviral protection is evident at 1 U/ml with FRTL cells, as opposed to 1000 U/ml for nonfunctioning rat thyroid (FRT) cells. Functioning FRTL thyroid cells are also more sensitive to mouse interferon (10-fold) with respect to 2',5'-polyadenylate (An) synthetase activity or to 125I-thyrotropin binding to membrane preparations than are nonfunctioning FRT cells. Antiviral protection in FRTL cells is evident as early as 1 h after exposure to mouse interferon, and is accompanied by a nearly 100-fold increase in the measurable titer of 2'5'-An synthetase activity. Actinomycin D blocks the antiviral effect of interferon, but not its effect on iodide uptake. The results are discussed with respect to the unusually sensitive response of heterologous (rat) cells to mouse interferon: a possible relationship between thyrotropin and interferon receptors; and, the difference in interferon sensitivity exhibited by differentiated (functioning) as opposed to undifferentiated (nonfunctioning) thyroid cells.

The effect of malignant transformation on the sensitivity of murine fibroblasts to the antiviral effect of interferon

The effect of malignant transformation on the sensitivity of murine fibroblasts to the antiviral effect of interferon

Antiviral effect of interferon in vivo may be mediated by the host.

INTERFERON has antiviral effects both in vivo and in vitro. Viral replication is inhibited in interferon-treated cells in vitro because the reproductive cycle of the virus is inhibited at the transcriptional or translational level, depending on the virus–cell system studied1. This direct inhibition of viral replication has been assumed to also be the mechanism by which interferon exerts its antiviral effect in vivo. We report here results that indicate protection by interferon against viral infection in vivo without inhibition of the viral replication of the same virus in vitro.

Differentiation of the immunosuppressive and antiviral effects of interferon

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 × 10 −5 M 2-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. 2-ME 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 2-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.

Enhancement of antiviral protection against encephalomyocarditis virus by a combination of isoprinosine and interferon.

The antiviral effect of interferon against encephalomyocarditis (EMC) virus infection in mice was enhanced by isoprinosine. However, the enhancement was only obtained when both interferon and the virus were inoculated into the peritoneum; the inoculation route of isoprinosone did not modify significantly the final results. In addition, the time sequence of injections was of great importance; generally the injection of isoprinosine had to precede that of interferon by a few hours.

Inhibition of Interferon Action by Cytochalasin B, Colchicine, and Vinblastine

SummaryCytochalasin B, colchicine, and vinblastine decrease the antiviral effect of interferon when added to cells simultaneously with interferon. The drugs are effective alone but their potency increases when used in combination. The lack of development of the antiviral state is observed without any detectable modifications in cellular RNA or protein synthesis. These drugs are known to disrupt microtubules and microfil-aments which are therefore probably necessary for interferon action. They could be involved in the distribution of membrane-associated receptors and/or in interactions between receptors and the cytoplasma. The initial steps leading to the establishment of antiviral protection by interferon could depend on these mechanisms.We thank Isabelle Tardivel for technical assistance and Carol Girard for help with the manuscript. Partial support came from the Delegation Generate a la Recherche Scientifique et Technique (Contract No. 74.7.0576).

Effects of Interferon on Cell and Virus Growth in Transformed Human Cell Lines

The anticellular and antiviral effects of human leukocyte interferons were studied in vitro in the transformed human embryonic cell lines. RSa and RSb. The growth of these cells was inhibited and they began to deteriorate about 48 h after treatment with 500 units/ml of interferon. When interferon was washed out within 48 h, their growth recovered gradually. The effects of interferon on cell growth depended on the amount of interferon added per cell. A subline, named IFr, was isolated which grows in the presence of 2000 units/ml of interferon, whereas growth of vesicular stomatitis virus in these cells is suppressed by 10 units/ml of interferon, just as in the parent cells. The anticellular and antiviral effects of interferon on IFr cells are discussed in relation to cell surface receptors.

The effect of ascorbic acid on production of human interferon and the antiviral activity in vitro.

The effects of ascorbic acid on interferon production and on the antiviral effect of interferon in cultures of human cells were investigated. Ascorbic acid enhanced the interferon levels produced by human embryo skin and human embryo lung fibroblasts, induced by Newcastle disease virus and by polyinosinic-polycytidylic acid. The same concentrations of ascorbic acid had no effect on interferon production in two lymphoblastoid cell lines induced by Sendai virus. Leucocyte interferon assayed in lung fibroblasts titrated 0.2-0.3 log10 units higher in the presence of 5 mug ascorbic acid than in the absence of the latter.