Showing papers on "Interferon published in 1971"
TL;DR: The semi-micro method for interferon assay was based on quantitation of inhibition of cytopathic effects in 6-mm wells and was more sensitive than the plaque-inhibition method and was extremely economical.
Abstract: Mostmethods ofinterferon assay, suchas plaque inhibition andyield reduction, areexpensive interms oftimeandmaterials. Lesscomplex methods, suchasinhibition ofcytopathic effects (CPE), tendtobesubjective anddifficult to quantitate. Finter (1)hasdescribed howcytopathology maybequantitated bytheuptake and elution ofavital dyeandhasapplied this technique totheassay ofinterferon. A micro-method fortitration ofhumanandchick interferon was described byTiles andFinland (4)whobased interferon activity on inhibition ofCPE,as observed inthemicroscope oron metabolic inhibition. This paper describes theassay ofrabbit interferon byasemi-micro, dye-binding method whichisextremely economical, especially in respect tocell culture materials andinterferon samples.
303 citations
TL;DR: Several other picornaviruses that failed to induce interferon in L cells, human embryonic lung cells, or monkey kidney cells did induceInterferon when these cells had been primed by homologous interferons, and priming appears to be a function ofinterferon separable from its antiviral activity.
Abstract: No interferon is made by L cells when they are infected with MM virus. However, several thousand units of interferon are produced when interferon-treated L cells are infected with MM virus. We call the conversion of cells, from nonproducers to producers, priming. The time required for cells to become fully primed is dependent on the interferon concentration with which they are incubated. Primed cells produced interferon earlier than normal cells stimulated by other inducers. Cells which were exposed to interferon in the presence of inhibitors of protein synthesis became fully primed yet developed no virus resistance. Also, primed cells produced interferon in response to low concentrations of polyriboinosinic acid · polyribocytidylic acid that did not induce interferon in normal cells. Therefore, priming appears to be a function of interferon separable from its antiviral activity. Several other picornaviruses that failed to induce interferon in L cells, human embryonic lung cells, or monkey kidney cells did induce interferon when these cells had been primed by homologous interferons.
201 citations
TL;DR: The kinetics of the production of the enhancing factor in mice injected with Newcastle disease virus was essentially identical to that of the simultaneous production of IF as measured by antiviral activity.
Abstract: Exposure of mononuclear cells from the mouse peritoneal cavity to interferon (IF)-containing mouse sera enhanced phagocytosis of colloidal carbon particles by the cells. The same effect was observed when the cells were exposed to IF-containing cell culture harvest free of serum. The magnitude of this effect of IF-containing preparations paralleled the titer of IF and was not related to the dilution of various IF-containing serum specimens tested. The factor responsible for the enhancing effect was stable at pH 2, inactivated by trypsin, and nonsedimentable at 105,000 × g. Heating at 60 C for 1 hr destroyed it, and its kinetics of heat inactivation paralleled that of the antiviral activity of IF. A period of incubation of phagocytic cells with IF-containing serum was necessary before a maximum level of enhancement was reached, and once established was not removable by repeated washing of cells. The kinetics of the production of the enhancing factor in mice injected with Newcastle disease virus was essentially identical to that of the simultaneous production of IF as measured by antiviral activity. Contrary to the effect of mouse IF preparations, human IF preparation did not enhance the activity of mouse phagocytes. It appears, therefore, that the phagocytosis-enhancing factor falls within the present definition of IF.
178 citations
TL;DR: These results, together with data reported previously, indicated that mononuclear cell invasion of infected liver foci, triggered by CMI, was of key importance in recovery from primary mousepox.
Abstract: Histological and immunofluorescence techniques showed that mononuclear cells invaded virus-infected foci in the livers of passively immunized mice within 10 hr of the receipt of immune spleen cells or hyperimmune serum; by 24 hr, marked destruction of virus antigens had occurred in these lesions. Immune cell transfer promoted denser packing of mononuclear cells in the foci and more efficient destruction of infectious material than immune serum. Similar liver lesions developed by the 6th day after sublethal, primary, subcutaneous infection in normal mice. In contrast, in mice with GVHR which were immunosuppressed but possessed hyperactive macrophages and unimpaired splenic interferon response, mononuclear cells did not invade liver lesions and the animals died. These results, together with data reported previously, indicated that mononuclear cell invasion of infected liver foci, triggered by CMI, was of key importance in recovery from primary mousepox. The roles of specifically sensitized lymphocytes and macrophages within lesions were not directly evaluated, but indirect evidence suggested that lymphocytes could cause no more than a halt in virus multiplication, and that macrophages were required for the inactivation of preformed virions. Possible augmentation of the efficiency of macrophages by locally-produced lymphocyte interferon, neutralizing antibody, or stimulation of their phagocytic and intracellular digestive capacity cannot be excluded.
167 citations
TL;DR: The results are interpreted to mean that recovery mechanisms conferred by immune spleen cells were triggered by specifically sensitized, thymus-derived lymphocytes, and that antibody and interferon responses were of less importance.
Abstract: The following passive transfer experiments evaluated the contributions of the various host responses in recovery from mousepox. (a) Immune spleen cells transferred highly efficient antiviral activity, but preinfected recipients of these cells made no detectable splenic interferon or antibody in the 24 hr interval after cell transfer. (b) Passively administered interferon was ineffective. (c) Recipients of hyperimmune serum had much more antibody than recipients of immune spleen cells but significantly less antiviral activity. (d) Immune spleen cell populations with antiviral activity contained mediators of CMI to virus antigens. (e) The antiviral activity of immune spleen cells was specific; it was inhibited by in vitro treatment with ATS, anti-light chain serum, and anti-theta ascitic fluid, but not by removal of mononuclear phagocytes from the immune population. These results are interpreted to mean that recovery mechanisms conferred by immune spleen cells were triggered by specifically sensitized, thymus-derived lymphocytes, and that antibody and interferon responses were of less importance. A radiosensitive recipient component was necessary for the full expression of the antiviral activity of both immune cells and immune serum. It seemed likely that this component was the blood monocyte.
157 citations
TL;DR: Although all cultures producing interferon showed some degree of transformation (thymidine-(3)H incorporation into deoxyribonucleic acid), no direct correlation between the degree of phytohemagglutinin-induced lymphocyte transformation and the interferons was observed.
Abstract: In studies of 13 normal adults to determine the blood cell types responsible for interferon production induced by phytohemagglutinin, the following observations were made. (a) In cultures containing 96-100% pure macrophages derived from blood monocytes, no interferon was detected in either the presence or the absence of phytohemagglutinin for up to 92 hr. (b) In cultures of 99.5-100% pure lymphocytes, low levels of interferon were detected in the presence, but not in the absence, of phytohemagglutinin. (c) An average fivefold increase in interferon titers occurred when pure lymphocytes were combined with the macrophages in culture with phytohemagglutinin. The peak response of interferon occurred at 68 hr after the initiation of the combined cultures. For maximum response, phytohemagglutinin was required for the duration of the culture, and both cell types in association were necessary. Medium from phytohemagglutinin-stimulated macrophages or lymphocytes could not substitute for the corresponding intact cell. However, frozen-thawed macrophages in combination with lymphocytes and phytohemagglutinin produced an intermediate interferon response. An increase in either cell type produced an increased response in the range studied: lymphocytes, 0.45-1.8 × 106 per ml; and macrophages, 0.5-2.1 × 105 per ml. Syngeneic fibroblasts, HeLa cells, or mouse macrophages could not substitute for the human macrophages in the combined cultures with phytohemagglutinin. (d) Although all cultures producing interferon showed some degree of transformation (thymidine-3H incorporation into deoxyribonucleic acid), no direct correlation between the degree of phytohemagglutinin-induced lymphocyte transformation and the interferon titers was observed.
The demonstration of macrophage-lymphocyte interaction in the production of interferon is of interest in view of the known interrelationship of these same cell types in antibody synthesis and cellular immunity.
142 citations
TL;DR: The particle-bound RNA polymerase activity of vesicular stomatitis virus (VSV) can be demonstrated in vivo and autoradiographs show the physical distribution, in cells, of RNA produced by virion polymerase in the absence of translation—a demonstration of the transcription product of the viral genome.
Abstract: The particle-bound RNA polymerase activity of vesicular stomatitis virus (VSV) can be demonstrated in vivo. Linear synthesis of viral RNA persists for 5 to 6 hours at 34°C in infected monolayers of chick embryo cells treated with cycloheximide and actinomycin D to block synthesis of protein and cell-specific RNA. At least 55 percent of the RNA made under these conditions is complementary to virion RNA. RNA synthesis mediated by VSV polymerase activity is inhibited in cells first treated with chick-derived interferon or polyriboinosinate• polyribocytidylate, but not by mouse interferon. The RNA product of VSV polymerase activity is present throughout the cytoplasm, and its synthesis is inhibited by the interferon system, as judged by autoradiographs that show the physical distribution, in cells, of RNA produced by virion polymerase in the absence of translation—a demonstration of the transcription product of the viral genome.
140 citations
TL;DR: A reproducible test system requiring small amounts of test compound was developed for evaluating antiviral and interferon-inducing activity and known active compounds evaluated in this microplate system had activity similar to that seen in macro in vitro systems.
Abstract: A reproducible test system requiring small amounts of test compound was developed for evaluating antiviral and interferon-inducing activity. In the antiviral experiments, KB cells were grown in disposable polystyrene microplates covered with a standard domestic plastic wrap. Viruses used in the system were types 1 and 2 herpes simplex virus, vaccinia virus, type 3 adenovirus, myxoma virus, pseudorabies virus, type 3 parainfluenza virus, types 1A and 13 rhinovirus, vesicular stomatitis virus, coxsackievirus B, and type 2 poliovirus. Inhibition of viral cytopathogenic effect was the primary criterion of evaluation of antiviral activity. Reduction in cell and supernatant fluid virus titers was used as a secondary means of evaluation. The microplate system was adaptable for determining prophylactic, therapeutic, and inactivating effects against viruses. Mouse L-929 cells were used for the interferon induction studies, with vesicular stomatitis virus utilized as the indicator of interferon activity. Known active compounds evaluated in this microplate system had activity similar to that seen in macro in vitro systems.
136 citations
TL;DR: It is postulated that inhibitors of protein synthesis suppress the accumulation of a cellular regulatory protein (repressor) which interacts with the interferon messenger ribonucleic acid mRNA and thereby prevents its translation.
Abstract: Low to moderate doses of cycloheximide had a stimulatory effect on interferon production in rabbit kidney cell cultures treated with double-stranded polyinosinate-polycytidylate (poly I:poly C). A very marked stimulation occurred in the presence of a dose of cycloheximide inhibiting amino acid incorporation into total cellular protein by about 75%. Higher doses of cycloheximide caused a shift in interferon release towards later intervals and a gradual decrease in the overall degree of stimulation. An even greater increase in the amount of interferon produced was observed if cells were treated with cycloheximide for only 3 to 4 hr immediately after their exposure to poly I:poly C. Under the latter conditions, a rapid burst of interferon production occurred after the reversal of cycloheximide action. Treatment with a high dose of actinomycin D before the reversal of cycloheximide action caused a further increase and a marked prolongation of interferon production. It is postulated that inhibitors of protein synthesis suppress the accumulation of a cellular regulatory protein (repressor) which interacts with the interferon messenger ribonucleic acid mRNA and thereby prevents its translation. Therefore, active interferon mRNA can apparently accumulate in rabbit kidney cells which, after exposure to poly I:poly C, are kept in the presence of an inhibitor of protein synthesis. Some of this accumulated interferon mRNA can be translated during a partial block of cellular protein synthesis, but its most efficient translation occurs after the reversal of the action of the protein synthesis inhibitor.
116 citations
TL;DR: The addition of macrophages to cultures of PPD-stimulated lymphocytes from tuberculin-sensitive individuals results in a greater than 3-fold increase in the production of interferon over that observed in cultures of lymphocytes or macrophage alone with PPD.
83 citations
TL;DR: This unexpected finding suggests either that the action of interferon involves inhibition of the transcription of early SV40 messenger RNA, or that the SV40 genome contains a "proto-early" gene whose product is required for thecription of the remaining early genes.
Abstract: Treatment with interferon reduced the content of early virus-specific RNA, as well as the content of an early viral protein (T antigen), in monkey cells acutely infected with simian virus 40 (SV40). This unexpected finding suggests either that the action of interferon involves inhibition of the transcription of early SV40 messenger RNA, or that the SV40 genome contains a “proto-early” gene whose product is required for the transcription of the remaining early genes.
TL;DR: Mouse interferon preparations inhibited the multiplication of mouse embryo and weanling mouse kidney cells in primary monolayer cell cultures and inhibited the proliferation of mouse MSV cells, sensitive to the anti-viral action of interferons, but did not affect themultiplication of cells of a subline, MSV-IF, resistant to theAnti-Viral activity of Interferon.
Abstract: SummaryMouse interferon preparations inhibited the multiplication of mouse embryo and weanling mouse kidney cells in primary monolayer cell cultures. A comparable inhibitory effect was also observed on the multiplication of cells of 2 established mouse cell lines. Both the anti-cellular and the anti-viral activities were markedly reduced by pretreatment of the interferon preparations with trypsin, sodium periodate or by heating at 60° for 1 hr. Mouse interferon preparations did not inhibit the multiplication of human KB cells. Human interferon preparations inhibited the multiplication of KB cells, but did not affect the multiplication of mouse cells. Mouse interferon preparations also inhibited the multiplication of mouse MSV cells, sensitive to the anti-viral action of interferon, but did not affect the multiplication of cells of a subline, MSV-IF, resistant to the anti-viral activity of interferon.
TL;DR: Mixed lymphocyte cultures from mice with marked differences in major and minor histocompatibility antigens were found to produce an inhibitor of viral replication with properties of interferon.
Abstract: Mixed lymphocyte cultures from mice with marked differences in major and minor histocompatibility antigens were found to produce an inhibitor of viral replication with properties of interferon. Cultures produced maximal amounts of interferon at approximately 72 to 96 hr, a time when maximal stimulation of deoxyribonucleic acid synthesis also occurred.
TL;DR: This chapter discusses that the discovery of interferon, a protein containing most of the common amino acids and some carbohydrate, including glucosamine, which may act by inhibiting the translation of viral messenger RNA.
Abstract: Publisher Summary This chapter discusses that the discovery of interferon Portions of the chorioallantoic membrane of embryonated chicken eggs is treated with heat-inactivated influenza virus for 3 hours, then incubated the membrane fragments in fresh solutions of buffered saline for an additional 24 hours When the fragments were removed, the solutions contained a substance that interfered with viral replication This antiviral substance was named as “interferon’’It could be quantitated by measuring the reduction in yield of infectious virus particles produced from membrane fragments pretreated with various dilutions of interferon prior to infection The antiviral activity was nondialyzable, sensitive to proteolytic digestion with trypsin stable at high and low pH, heat-stable, and insensitive to antibodies against the strain of influenza virus used to induce its formation The chapter also focuses on the properties of interferon that is physical, chemical, and biological It discusses that interferon is a protein containing most of the common amino acids and some carbohydrate, including glucosamine Disulfide groups, amino groups, and the methyl group of methionine are required for antiviral activity Substitution on sulfhydryl or hydroxyl groups does not affect biological activity Interferon is isoelectric at pH 65-70 but is stable from pH 2 to 10 The protein appears to have a molecular weight between 25,000 and 35,000, and hence is probably a single polypeptide chain It also reviews that interferon causes a stimulation of synthesis of an antiviral protein This antiviral protein may act by inhibiting the translation of viral messenger RNA
TL;DR: Krueger and Mayer have demonstrated production of interferon and protection against several viral infections in mice treated orally with apparently subtoxic doses of another low molecular weight compound: bis-DEAE-fluorenone.
Abstract: The production of interferon that is stimulated by a variety of microorganisms, microbial extracts, and synthetic polymers has been reviewed [1]. Most of these have a macromolecular structure, and only two substances of low molecular weight (cycloheximide, mol wt zz: 281, and kanamycin, mol wt izz 484) have ever been reported to stimulate production of interferon [2, 3]. The effect of the antibiotics was noted only at relatively high dosage levels and, with cycloheximide, interferon production was correlated with inhibition of protein synthesis [2]. More recently, Krueger and Mayer [4, 5] have demonstrated production of interferon and protection against several viral infections in mice treated orally with apparently subtoxic doses of another low molecular weight compound: bis-DEAE-fluorenone, also call tilorone hydrochloride
TL;DR: The results of experiments designed to test each of the possibilities for the inhibitory effect of interferon on the division cycle of L1210 cells are presented.
Abstract: We have previously described the inhibitory effect of interferon preparations on the multiplication of L1210 cells in vitro and presented the experimental results suggesting that interferon itself was the responsible factor (3, 4, 6) . This inhibition could be due to a decrease in the number of cells capable of dividing, to a prolongation of the cell generation time, to a decrease in the doubling potential of each cell between subcultivation and the stationary phase, or to a combination of these effects . We present here the results of experiments designed to test each of these possibilities by analyzing the effect of interferon on the division cycle of L1210 cells .
TL;DR: Evidence is presented which suggests that less of the template RNA of the UV-irradiation virus is copied and that the product which is synthesized is smaller than that synthesized by nonirradiated virus.
Abstract: Ultraviolet (UV)-irradiated Newcastle disease virus which has lost its infectivity but has the capacity to induce interferon also has the capacity to induce ribonucleic acid (RNA) synthesis both in vitro and early in infection in vivo. With large doses of UV irradiation, RNA-synthesizing capacity and interferon-inducing capacity are lost in parallel. Limited amounts of base-paired RNA associated with a transcriptive intermediate are involved in this RNA synthesis. These findings suggest the possibility that the single-stranded RNA of the UV-irradiated virus induces interferon by serving as a template for the synthesis of base-paired RNA. UV irradiation of the virus breaks down viral RNA but at a rate which is too slow to be a major cause of the loss of RNA-synthesizing capacity. Evidence is presented which suggests that less of the template RNA of the UV-irradiated virus is copied and that the product which is synthesized is smaller than that synthesized by nonirradiated virus.
TL;DR: The ability of reovirus to induce interferon formation in chick cells was less sensitive to irradiation with ultraviolet light than was its ability to produce infectious virus in L cells, suggesting that the interferons were induced by the double-stranded RNA of the inoculum virus.
Abstract: Summary
Treatment of chick cells with reovirus resulted in the production of an inhibitor of virus replication which was characterized as an interferon. No infectious virus was released, nor could any virus-specific RNA synthesis be detected in cells receiving virus. The ability of reovirus to induce interferon formation in chick cells was less sensitive to irradiation with ultraviolet light than was its ability to produce infectious virus in L cells. These data suggest that the interferon was induced by the double-stranded RNA of the inoculum virus. Comparison of this system with that induced by a synthetic double-stranded polynucleotide showed that the latter was considerably less sensitive to the effects of metabolic inhibitors, suggesting that the two inducers do not stimulate interferon formation by the same mechanism. The effect of addition of two metabolic inhibitors simultaneously to cells previously treated with a synthetic polynucleotide suggests that their effect is not a direct one on the formation of an interferon messenger RNA and its translation.
TL;DR: Cultures of primary mouse kidney cells and those of L cells produced interferon in response to Newcastle disease virus and polyinosinic-polycytidylic acid are suggested to contain two types of cells each of which responds uniquely to one type of inducer and each perhaps with its own distinct induction process.
Abstract: Summary
Cultures of primary mouse kidney cells and those of L cells produced interferon in response to Newcastle disease virus and polyinosinic-polycytidylic acid. The interferon produced by L cells was made between 8 and 18 hr post-inoculation irrespective of the inducer. The interferon produced by mouse kidney cell cultures in response to Newcastle disease virus was made between 8 and 18 hr while that produced in response to polyinosinic-polycytidylic acid was made between 2 and 12 hr.
Pre-treatment of L cells with interferon inhibited interferon production by both inducers, but pre-treatment of mouse kidney cell cultures inhibited only the 8 to 18 hr interferon stimulated by Newcastle disease virus. Thus the induction process stimulated by polyinosinic-polycytidylic acid was probably different in L cells from that in mouse kidney cells. On the basis of the time required to induce interferon production and the sensitivity of the induction process to the inhibitory effects of interferon pre-treatment, the induction process stimulated by polyinosinic-polycytidylic acid must be regulated differently in L cells and mouse kidney cells. The ability to stimulate interferon production repeatedly in mouse kidney cells by polyinosinic-polycytidylic acid indicated an induction process dependent only on the presence of an effective inducer.
Primary cultures of mouse kidney cells which produced good yields of interferon with polyinosinic-polycytidylic acid lost their ability to respond to this inducer after a single passage. Secondary cultures still responded to Newcastle disease virus, however. We suggest that primary cultures of mouse kidney cells contain two types of cells each of which responds uniquely to one type of inducer and each perhaps with its own distinct induction process.
TL;DR: Poly I:C (rIn:rCn), a synthetic double-stranded polynucleotide previously demonstrated to be a potent inducer of interferon and host resistance to viral infection in cell culture and in animals, has been successfully used to induce interferons in human beings.
Abstract: SummaryPoly I:C (rIn:rCn), a synthetic double-stranded polynucleotide previously demonstrated to be a potent inducer of interferon and host resistance to viral infection in cell culture and in animals, has been successfully used to induce interferon in human beings. Fourteen of 20 patients with advanced cancer developed interferon after a single intravenous administration of poly I:C. The interferon was identified by the usual criteria of pH stability, host species specificity, broad antiviral spectrum, inactivation by trypsin, and nonsedimentability under defined conditions. Several of the patients were capable of repeated induction of interferon by poly I:C at intervals of 3 to 7 days. Evidence of refractoriness to induction occurred only after repeated daily injections of poly I:C. The only consistent clinical manifestation of poly I:C administration was a febrile response. None of the patients tested developed demonstrable CF antibodies against either poly I:C or denatured DNA during the course of tre...
TL;DR: Treatment of ascites and solid tumors in mice with bovine enterovirus-1 resulted in regression of the tumors without any pathological effect on the animals, and death of mice with lymphatic-leukemia L4946 was delayed after such treatment.
Abstract: Treatment of ascites and solid tumors in mice (Sarcoma-1 and Ehrlich ascites carcinoma) with bovine enterovirus-1 resulted in regression of the tumors without any pathological effect on the animals. Death of mice with lymphatic-leukemia L4946 was delayed after such treatment. The oncolytic specificity of the virus does not appear to involve the production of interferon, but requires specific adsorption of virus to the tumor cells. The specificity of killing extends to cells in culture, since viral-transformed cells and oncogenic cells are susceptible to the virus, in contrast to cells of untransformed lines and cells of primary cultures, which are resistant.
The possibility of utilizing the specificity of nonvirulent viruses in therapeutic treatment of human cancers is considered.
TL;DR: Reovirus type 2 was found to adsorb to cells derived from a poikilothermic animal, the fathead minnow, and a state of viral resistance was developed and an antiviral substance was produced.
Abstract: SummaryReovirus type 2 was found to adsorb to cells derived from a poikilothermic animal, the fathead minnow. Although this interaction between cell and virus did not result in the production of infectious virus, viral antigen, or viral inclusion, a state of viral resistance was developed and an antiviral substance was produced. This viral inhibitor was shown to be interferon based on the possession of common characteristics.
TL;DR: Suppression of interferon production by uremic lymphocytes was not improved after peritoneal dialysis in one patient or after hemodialysis in 3 patients, but the depression of interFERon production was completely reversible in one patients after recovery from acute renal failure.
TL;DR: It is indicated that HSV-2 induced chromosome damage occurs in the absence of extensive viral DNA replication.
TL;DR: Mortality due to rabies was significantly reduced by the concurrent administration of 8 x 10(5) units of interferon divided between the site of virus inoculation and intravenously, and there was less protection if 3 hr elapsed between the inoculation of virus andInterferon.
Abstract: This study describes the effect of interferon on the survival of rabbits infected with a street strain of rabies virus. Interferon was prepared by collecting serum from rabbits injected with Newcastle disease virus and was characterized by biological and physicochemical methods. Rabbit serum interferon mixed and incubated with a suspension of rabies virus did not neutralize its infectivity. Rabbits were inoculated into the hind leg muscle with approximately 80 LD50 of virus. Interferon was administered intravenously or intramuscularly, or by both methods, in the same or opposite leg as virus. Mortality due to rabies was significantly reduced by the concurrent administration of 8 × 105 units of interferon divided between the site of virus inoculation and intravenously. There was less protection if 3 hr elapsed between the inoculation of virus and interferon. Treatment given 24 hr after infection did not prevent death but prolonged the incubation period.
TL;DR: Serial serum specimens collected prior to exposure and during the incubation period and acute phase of transfusion-associated hepatitis in 13 patients were tested for interferon, and none was found.
Abstract: SummaryNinety-six serial serum specimens collected prior to exposure and during the incubation period and acute phase of transfusion-associated hepatitis in 13 patients were tested for interferon. None was found. Two each of the patients had hepatitis-associated antigen, antibody to such antigen, or anticomplementary activity. Failure to detect interferon in hepatitis patients may be related to the tendency of viral hepatitis, in some cases, to become a prolonged or chronic disease.
Journal Article•
TL;DR: The colony inhibiting activity of whole serum is shown to be directly proportional to the interferon titre, and Interferon and colony inhibitor are also shown to have the same properties with regard to molecular size and sensitivity to heat, pH and trypsin.
Abstract: When mice are inoculated with Poly I—Poly C or influenza virus an inhibitor of haemopoietic colony forming cells appears in the serum. The colony inhibiting activity of whole serum is shown to be directly proportional to the interferon titre. Interferon and colony inhibitor are also shown to have the same properties with regard to molecular size and sensitivity to heat, pH and trypsin.
TL;DR: The results do not provide definitive evidence for or against the hypothesis that virus protein synthesis is inhibited at the translational level in the interferon-treated cell, and suggest that competition between endogenous and added messengers cannot be excluded in these systems.
Abstract: The activity of ribosome and cell-sap fractions from interferon-treated and control chick embryo fibroblasts was compared in mixed chick-mouse and purely chick cell-free systems capable of the synthesis of viral polypeptide(s) in response to viral ribonucleic acid (RNA). Interferon treatment of cells did not affect the intrinsic amino acid incorporation activity of these systems or their response to polyuridylic acid. With encephalomyocarditis (EMC) virus RNA as messenger, however, a fraction of the ribosomes from interferon-treated cells appeared less active than parallel controls. The results obtained with the corresponding cell-sap fractions were variable. Although competition between endogenous and added messengers cannot be excluded in these systems, a reduced level of translation of EMC RNA with interferon-treated cell ribosomes was also suggested by the results of analyses of tryptic digests of the products formed in response to the RNA. In addition, these analyses showed that this reduced activity must reflect a reduction in the rate or frequency of translation rather than a decrease in the length of the EMC RNA translated, for the same polypeptides were synthesized in response to the RNA with material from interferon-treated and control cells. Interferon added directly to the cell-free system was without effect. Although suggestive, these results do not provide definitive evidence for or against the hypothesis that virus protein synthesis is inhibited at the translational level in the interferon-treated cell. Possible alternative interpretations of the data are discussed.
Journal Article•
TL;DR: Using this delay in the onset of refractoriness, partial biologic separation of repressive activity from antiviral activity of interferon preparations was achieved and suggest a newly synthesized repressor as the mediator of theInterferon refractory state.
Abstract: Interferon synthesis is followed by a period of refractoriness during which restimulation with inducer fails to elicit an interferon response. This period persisted in mice absolutely for 4 days and partially for 13 days; interferon was initially induced with Newcastle disease virus (NDV) and animals were restimulated with an unrelated viral inducer. The development of refractoriness was found to be a graded function of the amount of inducer given and interferon made. Exhaustion of interferon-producing capabilities did not cause the refractory state; it developed both in vivo and in vitro after doses of NDV which elicited a less than maximal response. Furthermore, after an amount of inducer was given which was insufficient to infect all cells with complete infectious virus, refractoriness developed in cultures. In both mice and L cells refractoriness lagged significantly behind maximal interferon production; it was not discernible for 12 to 24 hr after measurable interferon response. Using this delay in the onset of refractoriness, partial biologic separation of repressive activity from antiviral activity of interferon preparations was achieved. Pretreatment of L cell monolayers with 75 units/ml of interferon preparations, collected 36 hr after inoculation of inducer, repressed interferon synthesis to a decidedly greater degree than those collected at 8 hr. Pretreatment of L cell monolayers with small amounts of interferon, 2 units/ml, enhanced interferon production to NDV. These findings suggest a newly synthesized repressor as the mediator of the interferon refractory state.