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At least 19 recordsLinked to original sources
PubMed1979

Studies on avian infectious bronchitis virus (IBV). III. Interferon induction by and sensitivity to interferon of IBV.

The induction of interferon by avian infectious bronchitis virus (IBV) and the sensitivity of IBV to interferon were studied. The results of experiments with ten IBV strains are summarized as follows. 1. All the IBV strains tested induced interferon in chick embryo (CE) cells, chicken kidney (CK) cells and embryonated eggs. The Iowa-609 strain induced about 1000 units of interferon in CE cells while the Beaudette-42 strain induced about 200 units of interferon in embryonated eggs; the interferon titers induced by other strains usually ranged from 5 to 60 units. No IBV strain induced interferon in HeLa or BHK-21 cells. 2. IBV particles inactivated by ultraviolet irradiation or by heating lost their ability to induce interferon. 3. The properties of the interferon produced in the present study are similar to those of other interferons produced in chicken cells. 4. HeLa or BHK-21 cells did not acquire resistance to virus infection, after incubation with interferon produced in CE cells. On the other hand, CK cells acquired the same degree of resistance to virus infection as CE cells after incubation with interferon produced in CE cells. 5. All the IBV strains tested were sensitive to interferon in CK cells. The sensitivities of Massachusetts-41 and Holte strains to interferon were similar to that of vesicular stomatitis virus.

Animals↗
PubMed1975

Circulating interferon in man after administration of exogenous human leukocyte interferon.

Interferon was measured at different intervals after the iv, sc, and im application of exogenous human leukocyte interferon to patients with various virus diseases or neoplasms. Interferon injected iv into patients had a half-life of about 15 minutes in the 1st hour and of about 90 minutes in the next 3 hours. Six hours after iv injection of 30 million U, no serum interferon was detectable. With a continuous iv infusion, a relatively high serum interferon level was reached. By the im administration of 1 million U interferon, a peak level of serum interferon (mean value 107 U/ml serum) occurred after 2 hours and was fairly stable for about 6 hours. Twenty-four hours after im application, a low level of serum interferon was still detectable. Similar results were found after sc interferon injections. In a patient with subacute sclerosing panencephalitis, no interferon was found in the cerebrospinal fluid at the time of the highest serum interferon level and 24 hours after two im interferon injections. Only minimal side reactions resulted from sc and im interferon injections. In one patient, a shock reaction occurred after iv application. For therapeutic trials, about 1 million U exogenous human interferon should be injected twice daily im or sc.

Encephalitis↗
PubMed1979

Interferon priming. Effects on interferon messenger RNA.

The effects of priming mouse cells with interferon on the production of interferon and its mRNA were investigated. Interferon-treated (primed) mouse L929 cells produce 3 to 10 times more interferon than do nonprimed cells following induction with Newcastle disease virus. Interferon appears 2 to 4 h sooner in the primed cultures than in nonprimed cultures and interferon production by primed cells becomes resistant to inhibition by actinomycin D about 4 h sooner than interferon production in nonprimed cells. Interferon mRNA is detected in primed-induced cells about 2 h earlier than in nonprimed-induced cells. It reaches peak levels about 2 to 4 earlier in primed cells, but it also disappears sooner in primed cells. The total amounts of interferon mRNA isolated from primed-induced cells and nonprimed-induced cells were indistinguishable, by the methods utilized. Therefore, although primed cells can produce significantly more interferon and make interferon mRNA sooner than nonprimed cells, the total amount of interferon mRNA produced is apparently not increased, nor is its half-life prolonged in primed cells. Thus, enhanced interferon production in primed cells may result from enhanced efficiency of translation of interferon mRNA in the primed cells.

Animals↗
PubMed1977

Interferon messenger RNA content of human fibroblasts during induction, shutoff, and superinduction of interferon production.

Translation of injected mRNA in oocytes of Xenopus laevis has been used as a highly sensitive and quantitative assay for interferon mRNA. Injection into oocytes of polyadenylylated RNA extracted from poly(I).poly(C)-induced human diploid fibroblasts (FS-4) leads to the synthesis of biologically active human fibroblast interferon over a period of 24-32 hr. There is a linear relationship between the amount of mRNA injected and the interferon yield obtained over a range of 1-20 ng of injected RNA. Injection of 40-80 ng of mRNA into each of 15 oocytes, homogenized in 0.3 ml of incubation medium, gave a titer of 128-256 interferon reference units/ml of homogenate.FS-4 cells at the peak of interferon production-i.e., approximately 2.5 hr after the beginning of induction with poly(I).poly(C)-gave mRNA that yielded 24-48 interferon reference units/ml in the oocyte assay (30 ng of RNA injected per oocyte). An equivalent amount of mRNA from FS-4 cells in the shutoff phase, approximately 6 hr after induction, gave </=4 interferon reference units/ml. In contrast, mRNA extracted from FS-4 cells that had been induced and maintained in the presence of 40 muM 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole for 6 hr produced 64-128 interferon reference units/ml. Polyadenylylated RNA obtained from uninduced FS-4 cells did not lead to detectable interferon synthesis (<4 interferon reference units/ml). These data provide a direct verification of the hypothesis that the shutoff of interferon production in FS-4 cells involves a regulatory event leading to the posttranscriptional inactivation or degradation of interferon mRNA. Because the inactivating mechanism is sensitive to inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, a selective inhibitor of nuclear heterogeneous RNA and mRNA synthesis, it is likely that synthesis of an RNA molecule is necessary for the shutoff of interferon production.

Animals↗
PubMed1978

Neutralizing antibodies against human leukocyte, lymphoblastoid and fibroblast interferons elicited by immunization with human leukocyte interferon.

Guinea pigs, rabbits, and sheep were immunized with partially purified human leukocyte interferon. The antisera were tested for their neutralizing activities against human leukocyte, lymphoblastoid (Namalva) and fibroblast interferons. Rabbits and sheep developed high levels of neutralizing antibodies against all three interferons. The ratios of the neutralizing activities of leukocyte/lymphoblastoid interferons varied from 1 to 25 and those of leukocyte/fibroblast interferons from 2 to 500. The ratios increased with prolonged immunization. The guinea pigs developed relatively low levels of anti-leukocyte and anti-lymphoblastoid antibodies and as a rule failed to produce detectable neutralizing activity against fibroblast interferon. One sheep was given a booster injection of fibroblast interferon after preimmunization with leukocyte interferon. The booster injection stimulated a rise in antibody levels, not only for fibroblast interferon, but also for leukocyte and lymphoblastoid interferons. The antigenic relationships between leukocyte, lymphoblastoid and fibroblast interferons are discussed.

Animals↗
PubMed1978

The mode of production of endotoxin-induced interferon in rabbit tissue cells. I. Development of priming by pretreatment with interferon.

In vitro production of endotoxin-induced interferon in rabbit tissue cell cultures could be enhanced by pretreatment with interferon. The enhancible state developed from the first hr of incubation at 37 C and a maximal priming effect was attained at 6 hr of incubation. Yields of interferon from unprimed cultures were usually 20-200 units/ml. In contrast, the primed cultures constantly yielded 1,000-2,500 units/ml of interferon. The pretreatment with interferon seemed to cause an earlier appearance of detectable interferon and the primed cells became more sensitive to endotoxin. It turned out that 10--30 units/ml of rabbit interferon were enough to develop the maximal priming. Even when cells were pretreated with higher doses of rabbit interferon such as 1.0 x 10(4) - 1.0 x 10(5) units/ml, the same level of priming effect was always observed without diminution. Various types of homologous (rabbit) and heterologous (human and mouse) interferon preparations showed similar dose-dependent enhancement of interferon production in proportion to the antiviral titers of these preparations as tested with RK-13 cells of rabbit origin.

Animals↗
PubMed1978

Interferon action III. The rate of primary transcription of vesicular stomatitis virus is inhibited by interferon action.

Transcription of vesicular stomatitis virus (VSV) in Vero cells was confined to the synthesis of parentally-derived mRNA (primary transcription) by the use of cycloheximide and/or a ts mutant, G41(IV), at a non-permissive temperature (40 degrees C). More transcripts accumulated in the presence of cycloheximide than in its absence. This so-called "cycloheximide effect" results from higher rates of virus transcription sustained for longer periods of time. The rate of VSV transcription initially increases linearly for 1 to 2 h after injection. Interferon reduces this rate (congruent to fourfold with 50 units/ml interferon) irrespective of the presence or absence of cycloheximide. The VSV mRNA transcripts synthesized in mock- or interferon-treated cells were equal in size and had an equivalent half-life of 17 h at 40 degrees C. It seems likely that once transcription is initiated in interferon-treated cells, it is completed successfully. Since interferon reduces the rate of early VSV primary transcript synthesis to below that achieved in the presence of cycloheximide, we conclude that interferon has an effect on transcription beyond that attributable solely to protein synthesis inhibition. We postulate that interferon decreases the probabiltiy of initiating virus transcription. Virus mRNA escaping this facet of interferon action may then encounter other facets such as post-transcriptional modification and/or inhibition of translation. However, the mandatory sequence of primary transcription leads to primary translation for negative-strand viruses like VSV dictates that the overall inhibitory effect of interferon on translation would derive in part from this prior inhibition of transcription. Thus, to apply the term "primary effect" to one particular facet of interferon action may not always be meaningful.

Cycloheximide↗
PubMed1979

Protection of mice against infection with wild-type Mengo virus and an interferon sensitive mutant (IS-1) by polynucleotides and interferons.

Single-stranded polynucleotide preparations [tRNA, poly(rI) plus poly(ho5C)-copolymer] which protect mice against picornavirus infections without inducing interferon, protected mice equally against infection with an interferon-sensitive mutant (IS-1) of Mengo virus and with wild-type virus (IS+). Poly(rI) . poly(rC), and mouse macrophage interferon [i.e. serum from mice treated with poly(rI) . poly(rC)] protected mice equally against infections with the two viruses, but fibroblast interferon protected better against infection with the interferon-sensitive mutant than with the wild-type virus. These and other results indicate that: Mengo virus had a genetic locus affecting sensitivity to fibroblast but not macrophage interferon; these two types of interferon have different mechanisms of action against Mengo virus infections in mice; Mengo virus genes controlling sensitivity to fibroblast interferon may modulate disease since infection in vivo induces only fibroblast interferon; the antiviral activity of the single-stranded polynucleotides is unlikely to be mediated by induction of either macrophage or fibroblast interferon.

Animals↗
PubMed1979

Interferon induction by viruses. II. Sindbis virus: interferon induction requires one-quarter of the genome--genes G and A.

We have measured the amounts of interferon formed by chick cells 'aged' in vitro in response to different amounts of infectious wild-type Sindbis virus. Our results suggest that one plaque-forming unit is enough to induce maximum interferon formation. With higher m.o.i. the yield of interferon is less. To inactivate the interferon-inducing activity of Sindbis virus, four times more u.v.-radiation was needed than to inactivate the infectivity of the virus. This suggests that only 25% of the virus genome need be intact in order to induce interferon. Temperature-sensitive Sindbis virus mutants from the three RNA+ complementation groups, C. D and E, gave rise to interferon in chick cells incubated at a non-permissive temperature, Similarly, mutants from two of the RNA- groups, B and F, gave rise to interferon, but not mutants from groups G and A. We conclude that no pre-formed inducer of interferon is present in Sindbis virus. It appears, however, that genes G and A represent a special one-quarter of the genome which must be functional in order to synthesize an interferon-inducing moiety. We suggest that this moiety is a double-stranded RNA molecule formed after synthesis of a segment of RNA complementary to the genome.

Animals↗
PubMed1976

Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. II. Studies with herpes simplex, Moloney sarcoma, vesicular stomatitis, Newcastle disease, and influenza viruses.

The effect of potent sheep anti-mouse interferon globulin was investigated in several different experimental virus diseases of mice. In anti-interferon globulin-treated mice infected intraperitoneally with herpes simplex virus (HSV) type I, the latent period was shortened, and the overall LD50 was increased several hundredfold compared to virus-infected control mice. When HSV was inoculated subcutaneously all anti-interferon globulin-treated mice died, whereas only 5% of virus-infected control mice died. Subsequent treatment with anti-interferon globulin of previously HSV-infected mice did not result in reactivation of HSV. Treatment of adult mice with anti-interferon globulin resulted in an earlier appearance of MSV-induced tumors, a greater number of mice bearing tumors, an increase in tumor size, and an increase in the duration of tumors. All tumors eventually regressed despite reinjection of anti-interferon globulin. Anti-interferon globulin treatment resulted in a rapid onset of disease and death in adult mice inoculated (intranasal) with VSV and in newborn mice infected with NDV. Anti-interferon globulin exerted no effect on the course of influenza virus infection of mice. We conclude that the early production of interferon is an importane element in the response of the mouse to several viruses exhibiting different pathogeneses.

Animals↗
PubMed1975

Are cytotoxicity and interferon inducing activity of poly(I).poly(C) invariably linked in interferon-treated L cells.

Interferon-treated L cells exhibit a specific enhanced susceptibility to the cytotoxic and interferon inducing activities of double-stranded RNAs such as poly(1). poly(C). These activities remained closely linked through widely varying assay conditions, involving, for example, different time anddosage schedules of poly(1). poly (C),suggesting that there is at least one common step in the mechanisms leading to interferon formation and toxicity in interferon-primed cells exposed to poly(1).poly(C). However, some procedures such as addition of metabolic inhibitors (actinomycin D, cycloheximide) and repeated administration of poly(1).poly(C) suppressed the interferon inducing capacity of poly(1).poly(C) without a concomitant decrease of toxicity. Other procedures such as brief treatment of the cells with interferon or DEAE-dextran permitted full expression of the interferon inducing activity of poly(1).poly(C) without any sign of toxicity. The latter results suggest that the mechanisms underlying interferon production and toxicity of poly(1).poly(C) in interferon-treated L cells diverge from a certain point onward.

Animals↗
PubMed1978

Purification of human interferon by antibody affinity chromatography, using highly absorbed anti-interferon.

Antibodies against partially purified human leucocyte interferon (PIF) were bound to Sepharose 4B and crude interferons applied on this affinity column were purified, up to 8 x 10(5) interferon units (IFU) per mg protein in one step. Antibodies against PIF were absorbed with immobilized crude human leucocyte interferon bound to Sepharose, whereby antibodies against impurities were predominantly removed. Extensively absorbed antisera were coupled to Sepharose and used for antibody affinity chromatography of crude interferon preparations. Leucocyte and fibroblast interferons were purified in one step with around 100% recovery, up to 1 x 10(8) IFU per mg protein, and Namalva interferon up to 2 x 10(7) IFU/mg. SDS electrophoresis of affinity-purified leucocyte interferon revealed that the interferon activity appeared in two bands (19,000 and 23,000 D).

Antibodies↗
PubMed1975

Characteristics of immune interferon produced by human lymphocyte cultures compared to other human interferons.

A factor with antiviral activity has been produced in vitro by combined macrophage-lymphocyte cultures from patients with recent herpes labialis in response to HSV antigen stimulation. It has been designated "immune interferon" and characterized in comparison to several other human interferons. It was shown to be relatively unstable at pH 2 and at 56 degrees C. Rabbit anti-human leukocyte interferon serum was shown to be less active against immune interferon than against diploid cell interferon or against vesicle fluid interferon. The possibility of immune interferon being a totally different anti-viral protein or a protein with certain shared antigen determinants or structures with classical viral interferon is discussed. A simplified method for the assay of anti-interferon sera with microtiter plates is also described.

Antigens, Viral↗
PubMed1977

Defense mechanisms against primary influenza virus infection in mice. I. The roles of interferon and neutralizing antibodies and thymus dependence of interferon and antibody production.

To investigate the defensive roles and production of interferon and antibodies, C3H/He mice were subjected to various immunosuppressive treatments and infected with influenza virus. In infected normal control mice the pattern of pulmonary viral growth can be divided into three phases. The first phase is characterized by an exponential increase of virus titer, the second by a rapid decrease, and the third by a moderate decrease. At the time of transition from the first phase to the second in pulmonary virus growth, interferon could be detected in the tracheobronchial washings of infected mice, but neutralizing antibodies could not. In infected B cell-deprived mice and infected anti-mu-treated mice, the transition from the first phase to the second occurred without any detectable antibody production, and interferon could be induced in the early stage of infection. However, the pulmonary virus in these mice increased again exponentially until the death of the mice. In infected T cell-deprived mice which could not induce interferon, but produced IgM-neutralizing antibodies, the second phase was not observed after the first phase, but a transient plateau phase could be demonstrated, and then the pulmonary virus increased again exponentially until the death of the mice. In anti-gamma-treated infected mice, pulmonary virus growth and production of interferon and neutralizing antibody were almost similar to those of infected normal control mice except for the absence of IgG neutralizing antibody production. Although anti-alpha-treated infected mice produced interferon and no IgA antibody, the transition from the first exponential increase of pulmonary virus to the second rapid decrease was seen, but then the virus increased exponentially again until the death of the mice. These results suggest that interferon plays an important role in the transition from the first phase to the second, and that T cells are required for interferon induction in mice infected with influenza virus. These data also suggest that IgA antibodies play an important role in the inhibition of virus propagation in the lungs after the disappearance of interferon. Moreover, infected T cell-deprived mice could produce only IgM neutralizing antibodies, but not IgG and IgA antibodies. Therefore, T cells are required for the production of IgG and IgA antibodies and even

Animals↗
PubMed1979

Mechanism of interferon action: phosphorylation of protein synthesis initiation factor eIF-2 in interferon-treated human cells by a ribosome-associated kinase processing site specificity similar to hemin-regulated rabbit reticulocyte kinase.

The phosphorylation of purified protein synthesis factors catalyzed by protein kinase preparations isolated from interferon-treated human amnion cells was examined. Ribosomal salt-wash fractions prepared from interferon-treated human cells contained a protein kinase that catalyzed the [gamma-(32)P]ATP-mediated phosphorylation of the 38,000-dalton subunit of eukaryotic initiation factor 2 (eIF-2alpha); this kinase activity was significantly enhanced in interferon-treated as compared to untreated cells. The tryptic [(32)P]phosphopeptide pattern obtained for eIF-2alpha phosphorylated by the interferon-mediated human kinase was indistinguishable from the pattern obtained for eIF-2alpha phosphorylated by the hemin-regulated rabbit reticulocyte kinase when analyzed by thin-layer chromatography with three different solvent systems and by high-voltage electrophoresis. O-[(32)P]Phosphoserine was liberated by partial acid hydrolysis from eIF-2alpha phosphorylated by either the human or the rabbit kinase. In addition to the phosphorylation of eIF-2alpha, interferon treatment of human cells enhanced the phosphorylation of two additional ribosome-associated proteins designated P(1) and P(f). The major phosphoester linkage observed for the human, as well as murine, phosphoprotein P(1) was O-phosphoserine. The interferon-mediated phosphorylation of both eIF-2alpha and protein P(1) was dependent upon the presence of RNA with double-stranded character; P(f) phosphorylation was not affected by double-stranded RNA. These results suggest that the interferon-mediated ribosome-associated human protein kinase catalyzes the phosphorylation of eIF-2alpha in a site-specific manner that is apparently identical with the reaction catalyzed by the hemin-regulated rabbit reticulocyte kinase; hence, the phosphorylation of eIF-2 may play a role in regulating the initiation of translation in interferon-treated cells.

Cells, Cultured↗
PubMed1976

Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection.

The role of interferon in the pathogenesis of encephalomyocarditis (EMC) virus infection was determined by treating mice with potent, partially purified sheep anti-mouse interferon globulin. In control mice, EMC virus was present in low titers in various visceral organs but attained high titers in the brain towards the 4th to 5th day, at which time mice died with signs of central nervous system disease. In mice treated with anti-mouse interferon globulin, virus was present in high titer in visceral organs 24--36 h after viral inoculation and virtually all mice were dead by 45 h. This rapid evolution of EMC virus infection was not observed in mice treated with the globulin fraction prepared from a normal sheep, from a sheep exhibiting a low anti-mouse interferon-neutralizing titer, nor from a sheep having a high titer of antibody to human leukocyte interferon. The experimental results indicated that anti-interferon globulin neutralized the interferon liberated by virus-infected cells, thus permitting extensive virus multiplication in several visceral organs. We conclude that interferon is an important early component of host resistance to this virus infection.

Antigen-Antibody Complex↗
PubMed1975

Cyclic AMP potentiation of interferon antiviral activity and effect of interferon on cellular cyclic AMP levels.

Treatment of L cells with 3 to 10 mM 3':5'-cyclic adenosine monophosphate (cAMP) in the presence of interferon was found to potentiate the development of antiviral activity. The dose response of interferon activity at various time periods in the presence and absence of cAMP indicated that potentiation of interferon activity by cAMP occurred at an early stage in the development of antiviral activity. Among the analogues of cAMP tested for interferon-potentiating activity, only the acylated derivatives were found to be active. Combined L-epinephrine and theophylline treatment of cells elevated cellular cAMP levels and also potentiated interferon-mediated antiviral activity. Interferon was also found to elevate cAMP levels in L cells. This activity was limited to biologically active interferon and antagonized the depression of cAMP associated with vesicular stomatitis virus (VSV) infection of L cells. These observations suggest that some aspects of interferon's biological activity is associated with an alteration in cellular levels of cAMP.

Animals↗