Showing papers on "Interferon published in 1974"
Book•
01 Jan 1974
TL;DR: A definition of a virus and some methods for studying animal viruses, as well as the classification and nomenclature of viruses, are presented.
Abstract: Preface Towards a definition of a virus How to handle animal viruses The structure of viruses Viral nucleic acids The process of infection I: Attachment and penetration The process of infection IIA: The Baltimore classification The process of infection IIB: The replication of viral DNA The process of infection IIC: RNA synthesis by RNA viruses The process of infection IID: RNA viruses with a DNA intermediate and vice versa The process of infection III: The regulation of gene expression The process of infection IV: The assembly of viruses Lysogeny Interactions between viruses and eukaryotic cells The immune system and interferon Virus-host interactions Vaccines and chemotherapy: the prevention and treatment of virus diseases Carcinogens and tumour viruses The evolution of viruses HIV and AIDS Trends in virology The classification and nomenclature of viruses
234 citations
TL;DR: It is reported here that human leukocyte and fibroblast interferon preparations exert a pronounced antiviral activity on bovine and porcine cells, and the activity of the humanLeukocyte interferons is far greater on heterologous bovin cells than on homologous human or monkey cells.
Abstract: INTERFERONS prepared from cells of one species may exhibit some activity on cells of others although the titre on heterologous cells is usually considerably lower than that for homologous cells1. The one exception to date has been the finding that human fibroblast interferon was far more active on heterologous rabbit cells than on human cells2,3. We report here that human leukocyte and fibroblast interferon preparations exert a pronounced antiviral activity on bovine and porcine cells, and the activity of the human leukocyte interferon is far greater on heterologous bovine cells than on homologous human or monkey cells.
190 citations
Journal Article•
TL;DR: It was found that in “low-responder” composite cultures, pretreatment of the B cell population with low amounts of interferon led to a considerable enhancement of the antibody response, whereas higher concentrations of Interferon gave a similar degree of inhibition as that found for “high-responding” cultures.
Abstract: Mouse interferon preparations inhibited the antibody response to sheep erythrocytes (SRBC) in spleen cell cultures. The effect was seen when the cultures were pretreated with interferon for 6 hr, or when interferon was added up to 40 hr after addition of SRBC. The factor responsible for this inhibition could not be dissociated from the antiviral activity of interferon by standard physicochemical means. The application of a mosaic cell culture system suggested that the inhibitory effect of interferon was due to an action on B cells. Interferon treatment of T cells and macrophages did not affect their normal function as helper cells in this system. To our knowledge, these findings constitute the first example of an effect of interferon on B lymphocytes. In addition, it was found that in “low-responder” composite cultures, pretreatment of the B cell population with low amounts of interferon led to a considerable enhancement of the antibody response, whereas higher concentrations of interferon gave a similar degree of inhibition as that found for “high-responder” cultures. Late addition of mouse interferon preparations to SRBC-stimulated spleen-cell cultures augmented the number of plaque-forming cells (PFC). This effect was most pronounced when interferon was added only 4 hr before the plaques were counted on day 4. This increase was followed on day 5 by a decrease in the number of PFC compared with that of control cultures.
174 citations
TL;DR: The production of viral dsRNA in response to infection could bring about a general inhibition of protein synthesis in the interferon-treated cell, as is indeed observed in interferons-treated, vaccinia virus-infected mouse fibroblast L cells.
Abstract: NATURALLY occurring and synthetic double-stranded RNAs (dsRNAs) are interferon inducers1. They inhibit protein synthesis in animal cells2 and cell-free systems3–5. It is intriguing, therefore, that interferon treatment renders cells more sensitive to the toxic effects of dsRNA6, particularly as viral dsRNA may be involved in the replication of RNA viruses and has been isolated from DNA virus-infected cells7. Accordingly, the production of viral dsRNA in response to infection could bring about a general inhibition of protein synthesis in the interferon-treated cell, as is indeed observed in interferon-treated, vaccinia virus-infected mouse fibroblast L cells8,9. The cell dies but little virus is produced: an effective way of limiting a natural infection.
168 citations
TL;DR: It was found that the inducing virus could be recovered at the end of the adsorption period and reutilized at least seven times without loss of its interferon inducing capacity.
Abstract: SummaryA method has been described for the large scale production of potent mouse interferon preparations based on the cultivation and induction of cells in suspension culture. By the selective use of metabolic inhibitors and the choice of optimal culture conditions, large quantities of interferon titering 4 × 105 mouse reference units/ml (specific activity 106 reference units/mg of protein), were consistently obtained. It was found that the inducing virus could be recovered at the end of the adsorption period and reutilized at least seven times without loss of its interferon inducing capacity. Although this method has been described for the production of mouse interferon using C243-3 cells it is applicable to the production of human or other interferons from cells which multiply in suspension culture.We are indebted to Mrs. J. Buywid and Mrs. M. T. Bandu for their skilled technical assistance, and to Dr. S. Baron, NIH, Bethesda, for the gift of the C243-3 cells. M.G.T. is indebted to the Fondation Philip...
167 citations
TL;DR: The data suggest that membrane sites interacting with interferon are carbohydrate-containing molecules that bind to PHA, although other explanations for the inhibitory action of PHA based on nonspecific steric or charge effects might be possible.
Abstract: RECENT evidence suggests that the antiviral action of interferon is triggered by interaction with the cellular membrane. Mouse interferon covalently bound to Sepharose beads (IF-Sepharose) retains its antiviral potency and only direct contact with these particles produces the antiviral effect1,2. Preincubation of mouse L cells with Phaseolus vulgaris phytohaemagglutinin (PHA) blocks interferon action3. The inhibitory action of PHA can be almost completely reversed by washing PHA-treated cells with fetuin, a glycoprotein of high affinity for this plant lectin3. These data suggest that membrane sites interacting with interferon are carbohydrate-containing molecules that bind to PHA, although other explanations for the inhibitory action of PHA based on nonspecific steric or charge effects might be possible. To substantiate further that glycoside-containing membrane components bind to interferon, we have investigated the effect of gangliosides on interferon binding and action.
163 citations
TL;DR: Macrophages appear to be essential for the uptake and processing of tumor antigens preceding the initiation of an effective immune response, and direct macrophage-mediated antitumor activity appears to contribute significantly to host survival and deserve careful consideration in both the experimental and clinical study of animal and human neoplastic disease.
Abstract: Publisher Summary This chapter reviews the role of macrophages in defense against neoplastic disease. Macrophages do exert both natural and adjuvant-stimulated, afferent and efferent antineoplastic activities. Macrophages appear to be essential for the uptake and processing of tumor antigens preceding the initiation of an effective immune response. Additionally, the macrophage alteration of antigen may promote successful immunization as opposed to the induction of tolerance or production of enhancing or blocking factors. The macrophage might further enhance the immune response by stimulating the proliferation of immunocompetent cells through the production of lymphocyte-activating factor (LAF) or the delivery of macrophage-contained adjuvant. Aided by cytophilic antibody, specific macrophage arming factor (SMAF), macrophage migration inhibitory factor (MIF), interferon, nonspecific opsonins, or nonspecific activation, macrophages, either alone or in concert with other immune cells, can exert both immune and nonimmune cytotoxicity toward neoplastic cells. This antitumor activity is most likely mediated through a nonphagocytic, contact-dependent mechanism, associated in only a few systems with the release of soluble toxic substances. Such direct macrophage-mediated antitumor activity, as well as macrophage-mediated induction and the amplification of antitumor immune responses, appear to contribute significantly to host survival and deserve careful consideration in both the experimental and clinical study of animal and human neoplastic disease.
149 citations
Journal Article•
TL;DR: Antigen-stimulated lymphocyte transformation, as measured by 3H-thymidine incorporation, and interferon production were studied serially in humans after Herpes virus hominis (HSV) disease and appeared to reflect prior immune status rather than acute infection.
Abstract: Antigen-stimulated lymphocyte transformation, as measured by 3H-thymidine incorporation, and interferon production were studied serially in humans after Herpes virus hominis (HSV) disease. Lymphocytes were isolated by filtration through a nylon fiber column and added to isologous macrophage cultures prepared 1 week previously. Macrophage-lymphocyte interaction was required for optimum interferon production. A selective increase in interferon production was associated with disease occurrence in some individuals. The increase in interferon production by lymphocytes was maximum between 2 and 6 weeks after disease. In contrast, lymphocyte transformation and serum antibody levels were similar throughout a 12-week period after disease and appeared to reflect prior immune status rather than acute infection. Some subjects with HSV disease failed to produce a detectable interferon response within the 2- to 6-week period after disease. In these individuals, lesion recurrence was more frequent when compared to subjects producing greater quantities of interferon after disease.
139 citations
TL;DR: The differential response in trisomnic 21 cells is consistent with the known assignment of the human antiviral gene to chromosome 21.
Abstract: Human primary skin fibroblasts trisomic for chromosome 13, 18, or 21 and diploid human skin fibroblasts were induced for an antiviral response with human interferon. The cells that were trisomnic for chromosome 21 were three to seven times more sensitive to protection by human interferon than the normal diploid or trisomic 18 or 13 fibroblasts. The differential response in trisomnic 21 cells is consistent with the known assignment of the human antiviral gene to chromosome 21.
136 citations
TL;DR: The results suggest that the antiviral activity of interferon is mediated, at least in part, by a ribosome-associated polypeptide that permits discrimination between cellular and viral mRNAs.
122 citations
TL;DR: T cells or T cell products are ineffective in inducing or accelerating B cell interferon or proliferative response at 3 days, and the use of 3-day T cell Interferon production as a new technique for the assessment of T cell effector function and competence is suggested.
TL;DR: The average level of circulating interferon attained by either the im or iv route was higher than reported levels in naturally occurring human viral diseases and was approximately 17 times the minimal inhibitory concentration for varicellazoster virus in human cell culture.
Abstract: levels > 100 units/ml were obtained more rapidly and were sustained longer after im administration. When an injection was given im on three successive days, peak daily titers rose progressively, suggesting accumulation in tissues. The rate of rise of varicella-zoster complement-fixing antibodies and the titers of interferon in vesicular fluid and cell counts in the patients treated with interferon did not differ significantly from those of a group of control patients. The only adverse side effect of treatment with interferon was fever of 38 C-40 C after injections. Assays of cerebrospinal fluid and urine specimens generally failed to demonstrate significant titers of interferon during periods when serum levels were known to be >100 units/ml. The average level of circulating interferon attained by either the im or iv route was higher than reported levels in naturally occurring human viral diseases and was approximately 17 times the minimal inhibitory concentration for varicellazoster virus in human cell culture.
TL;DR: Mouse interferon preparations enhanced the expression of histocompatibility antigens of thymocytes from mice of different ages, but of splenic lymphocytes only from young mice.
Abstract: The expression of surface antigens of thymocytes and splenic lymphocytes was determined by quantitative absorption of alloantibodies. Mouse interferon preparations enhanced the expression of histocompatibility antigens of thymocytes from mice of different ages, but of splenic lymphocytes only from young mice. Interferon did not affect the expression of the theta antigen of thymocytes or splenic lymphocytes.
TL;DR: Interferon treatment in AKR cells inhibited the assembly or release of the virus, and intracellular levels of viral groups-specific antigens were significantly increased.
Abstract: Treatment of AKR cells that had spontaneously become procedures of a murine leukemia virus with a partially purified mouse interferon (> 5 × 107 international mouse reference units per mg of protein) inhibited endogenous virus production. This inhibitory effect decreased over a 72-hr period in a manner similar to interferon-induced antiviral activity directed against vesicular stomatitis virus in AKR cells. Despite the inhibitory effect of interferon on infectious murine leukemia virus and viral reverse transcriptase (RNA-dependent DNA polymerase) titers in the culture fluids, intracellular levels of viral groups-specific antigens were significantly increased. These results suggest that interferon treatment in AKR cells inhibited the assembly or release of the virus.
Journal Article•
TL;DR: Swiss-Webster mice injected intravenously with interferon preparations 2 days before primary or secondary immunization with sheep erythrocytes showed a significant suppression of their hemolysin and agglutinin responses as measured in microtiter assays, suggesting inhibition of the immune response by Interferon is significant in the immunosuppression observed during viral infection or after administration of nonspecific mitogens.
Abstract: Swiss-Webster mice injected intravenously with interferon preparations 2 days before primary or secondary immunization with sheep erythrocytes showed a significant suppression of their hemolysin and agglutinin responses as measured in microtiter assays. Interferon treatment in vivo also inhibited DNA synthesis induced in mouse lymphocytes studied in vitro by concanavalin A, phytohemagglutinin, and lipopolysaccharide. In addition, it suppressed the in vitro primary and secondary response to sheep erythrocytes. It is possible that this inhibition of the immune response by interferon is significant in the immunosuppression observed during viral infection or after administration of nonspecific mitogens, or perhaps even in the control of the normal immune response.
Journal Article•
TL;DR: It is suggested that peripheralized T cells are required for interferon production after mitogen stimulation, and spleen cells, a mixture of B and T cells, were treated with anti-K chain serum and complement and then stimulated with PHA.
Abstract: The cell population necessary for interferon production after mitogen stimulation was investigated in the mouse. Thymus cells and cortisone-resistant thymus cells failed to produce interferon after mitogen stimulation. When spleen cells, a mixture of B and T cells, were treated with anti-K chain serum and complement and then stimulated with PHA, no diminution of interferon production was observed. However, when spleen cells were treated with anti-ϑ antibody and complement and then stimulated with PHA, interferon production was markedly reduced. These studies suggest that peripheralized T cells are required for interferon production after mitogen stimulation.
TL;DR: Interferon treatment of murine C‐type oncornavirus carrier lines results in a drastic inhibition of extracellular virus formation but cell‐associated virus as seen in the electron microscope or as detected by uridine incorporation is not proportionally inhibited.
Abstract: Interferon treatment of murine C-type oncornavirus carrier lines results in a drastic inhibition of extracellular virus formation. When such cells are subcultured in the presence of interferon, synthesis of extracellular C-type virus remains depressed until the interferon treatement is discontinued. Cell-associated virus as seen in the electron microscope or as detected by uridine incorporation is not proportionally inhibited. Several possibilities to explain this discrepancy are tested. The most likely hypothesis is that interferon treatment primarily inhibits virus release.
TL;DR: Partially purified human leukocyte interferon suppressed the in vitro response of human lymphocytes to phytohaemagglutinin, and purified protein derivative and also the mixed lymphocyte reaction.
Abstract: Partially purified human leukocyte interferon suppressed the in vitro response of human lymphocytes to phytohaemagglutinin. concanavalin A, and purified protein derivative and also the mixed lymphocyte reaction. The inhibitory effect correlated with concentration and was detectable at 10 units/ml of culture medium. The activation of lymphocytes by pokeweed mitogen was affected by interferon only in very high concentrations The data presented are considered to be of clinical importance, since the serum interferon levels in patients receiving therapy with such preparations exceed the concentrations required for detection of in vitro inhibition of mitogenic stimuli.
TL;DR: Lead increased the response of the mice to all classes of viruses against which it was tested and represses the anti-EMCV protective effects of both PIC and of NDV, which, in other reports, were shown to induce IF in radioresistant macrophages or in radiosensitive lymphocytes.
Abstract: Lead acetate was administered continuously in the drinking water to CD–1 male mice beginning at 4 weeks of age. An LD10–20 of the lytic viruses or 300 plaque-forming units of RLV was inoculated int...
TL;DR: The fibroblast product, in contrast to interferon from leukocytes, could only be harvested efficiently from the crude starting material when a carrier protein was added to the eluting buffers to counteract losses, presumably due to adsorption on purification and assay equipment.
Abstract: Human interferon prepared by challenge of leukocytes with Sendai virus, or of fibroblasts with double-stranded poly(inosinic acid)·poly(cytidylic acid), has been studied with respect to purification by affinity chromatography. Both leukocyte and fibroblast interferons are removed from crude tissue culture fluids by means of columns of antibody to leukocyte interferon attached to Sepharose-4B. The antibody was prepared in sheep using, as antigen, material that had been partially purified by gel filtration through Sephadex G-100 columns. Many of the impurities in the crude fibroblast interferon were presumably not recognized by the sheep antibodies induced by leukocyte interferon. Fibroblast interferon was, therefore, much more effectively purified as the result of this “common denominator” approach. The fibroblast product, in contrast to interferon from leukocytes, could only be harvested efficiently from the crude starting material when a carrier protein (bovine-serum albumin, and later, cytochrome c) was added to the eluting buffers to counteract losses, presumably due to adsorption on purification and assay equipment. Both varieties of interferon exhibit molecular weights of approximately 20,000-25,000, although association with higher molecular weight proteins occurs.
TL;DR: It is shown that an inhibitor of translation, which appears to be a protein associated with the ribosomes, accumulates in extracts of interferon treated L cells and can be eliminated by the addition of purified fractions of mammalian transfer RNA.
TL;DR: The results reveal the selective nature of the inhibition of protein accumulation in interferon-treated, virus-infected cells and indicate that the selectivity of the effect in vivo is not well reflected in vitro.
TL;DR: Results are interpreted as indicating that inhibition of virus development by interferon does not act at the level of primary transcription but rather at an intermediate step between primary and secondary transcription, such as viral protein synthesis.
Abstract: The synthesis of viral complementary RNA by vesicular stomatitis virus in permissive cells can be distinguished operationally into two phases, primary transcription, which can be observed in cycloheximide treated cells, and secondary transcription, which represents the further synthesis of viral complementary RNA obtained in untreated cells. Pretreatment of mouse L cells or chicken embryo fibroblasts with the homologous interferon and, for chicken embryo fibroblast cells, poly(rI):poly(rC), inhibits the production of infectious virus and reduces the synthesis of viral complementary RNA to levels comparable to that obtained during primary transcription. Treatment of mouse L cells with interferon plus cycloheximide also gives levels of vesicular stomatitis viral complementary RNA synthesis comparable to that observed with the cycloheximide treatment alone. Similar results have been obtained for interferontreated cells subsequently infected with influenza virus (strain WSN). The results are interpreted as indicating that inhibition of virus development by interferon does not act at the level of primary transcription but rather at an intermediate step between primary and secondary transcription, such as viral protein synthesis.
TL;DR: The concept that the cellular immune response to HSV consists of two phases: an immunologically specific antigen recognition phase, and a nonspecific effector phase that stops HSV spread by generating interferon is supported.
Abstract: Rabbit kidney cell monolayers infected with herpes simplex virus (HSV) were incubated with leukocytes from rabbits immunized with complete Freund's adjuvant. When the leukocytes were exposed to tuberculin purified protein derivative (PPD), viral replication and plaque formation were markedly inhibited. Similarly, when leukocytes from animals immunized with HSV were exposed to UV-inactivated HSV, viral replication was markedly inhibited. Exposure of leukocytes from unimmunized animals or animals immunized with incomplete Freund's adjuvant to UV-inactivated virus or PPD produced relatively little inhibition of viral replication. Examination of supernatant fluids from stimulated cultures revealed a soluble mediator that had the properties of interferon. Interferon production was detected within several hours after exposure of sensitized leukocytes to antigen. Supernatant fluids from as few as one sensitized leukocyte per 200 rabbit kidney cells inhibited HSV replication by over 90%. These findings support the concept that the cellular immune response to HSV consists of two phases: an immunologically specific antigen recognition phase, and a nonspecific effector phase that stops HSV spread by generating interferon.
TL;DR: It was shown that the efficiency of cytotoxicity was inversely related to spleen cell density, which was interpreted to mean that thymus‐derived (T) cells, probably acting alone, were responsible for cytot toxicity and that the mechanism involved contact between T cell and target cell.
Abstract: Cell-mediated cytotoxicity of ectromelia-immune spleen cells against ectromelia-infected L929 target cells was abrogated by treatment of the spleen cells with anti-Θ antibody and complement. Treatment of spleen cells with anti-immunoglobulin serum and complement, or removal of macrophages had little or no effect on cytotoxicity. Specific or nonspecific soluble cytotoxic factors were not detected, and exogenous interferon did not enhance cytotoxicity. No blocking of cytotoxicity was detected with either hyperimmune or 9-day immune anti-ectromelia serum. By varying the spleen cell-target cell ratio from 3: 1 to 400: 1, it was shown that the efficiency of cytotoxicity was inversely related to spleen cell density. These results were interpreted to mean that thymus-derived (T) cells, probably acting alone, were responsible for cytotoxicity and that the mechanism involved contact between T cell and target cell.
TL;DR: It is postulated that interferon induction is dependent on a low threshold level of RNA synthesis occurring early in infection as well as on the input multiplicity of the virus.
Abstract: Summary
Interferon induction by 11 temperature-sensitive (ts) mutants of the HR strain, and 38 ts mutants of the AR339 strain of Sindbis virus was investigated. All HR and AR339 mutants induced interferon at 30 °C. Induction by the mutants at the restrictive temperature (39 °C) was dependent on the time of incubation, and, in some instances, on the input multiplicity. At an input multiplicity of 5, and after an incubation time of 16 h at 39 °C, induction by the AR339 mutants was dependent on virus RNA synthesis. All HR mutants showing detectable RNA synthesis at 39 °C induced interferon, but of those showing undetectable RNA synthesis at 39 °C, three induced interferon and three did not. At 42 °C, RNA synthesis by the HR wild-type and all ts mutants was depressed, and only one mutant and the wild type induced interferon. Temperature shift experiments showed that interferon induction was dependent on an early virus function. It is postulated that interferon induction is dependent on a low threshold level of RNA synthesis occurring early in infection.
TL;DR: It was found that in monkey cells both the viral transcription and viral translation were reduced by the same rate by human interferon, which supports the hypothesis that the SV40 genome transcription is primarily affected by interferons.
TL;DR: Cellular immunity to the varicella-zoster virus can be studied in relation to the risk of infection in immunosuppressed patients, and such work may lead to a better understanding of the phenomenon of latency.
Abstract: Lymphocytes obtained from nonimmune children and from adults after an attack of herpes zoster were incubated with antigens of varicella-zoster virus. Lymphocyte transformation, measured by the incorporation of tritiated thymidine, was found to reflect specific immunity to the varicella-zoster virus, although the degree of transformation could not be related to the activity of the disease. Production of interferon was dependent on the method of preparation of lymphocytes and was not related to disease activity or to the immune status of the donors. The interferon-producing and DNA-synthesizing activities could be dissociated by antigen dilution, further suggesting that production of interferon was nonspecific. The extent of immune-specific incorporation of tritiated thymidine by lymphocytes could be increased by incubation of the cultures in the presence of fetal calf serum. Cellular immunity to the varicella-zoster virus can be studied in relation to the risk of infection in immunosuppressed patients, and such work may lead to a better understanding of the phenomenon of latency.