Interferon Responses of Chick Embryo Fibroblasts to Nucleic Acids and Related Compounds

Jensen, Keith E.; Neal, Alan L.; Owens, Ralph E.; Warren, Joel

doi:10.1038/200433a0

Cited by 64 publications

(19 citation statements)

References 2 publications

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“…Furthermore, Isaacs et al's hypothesis that cells recognize exogenous nucleic acid as foreign or self was made incompatible, since oligonucleotides of relatively low molecular weight derived fom the "self" RNA were found to be a good inducer of interference. Second, in the work of Jensen et al [16], who reported If production stimulated by commercial yeast RNA and other nucleic acids, as well as mononucleotides, chick embryo fibroblasts were incubated for several weeks, raising the possibility that some contaminant, such as occult viruses, or some substances from degenerated cells might have been the actual stimulus for If production. On the other hand, protection of mice from influenza virus by nucleic acid reported by the same group [24] appears to involve a mechanism other than If production, and might have something in common with the present findings.…”

Section: Discussionmentioning

confidence: 99%

“…Inquiry into the nature of the essential stimulus for If induction led Isaacs et al [15,23] to a proposal that cells respond to foreign nucleic acid by production of If. This hypothesis, attractive as it is, does not seem to have since been substantiated [13,14], in spite of a seemingly corroborative report [16]. Interest in nucleic acid as an inducer of If synthesis and cellular resistance has revived by recent studies of Lampson and collaborators, who showed that double-stranded RNA's from various sources, but not single-stranded RNA's, are potent inducers in rabbits and in mice [7,8,19,25].…”

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confidence: 99%

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Interference with Virus Infection Induced by RNA in Chick Embryo Cells

Fukada

Kawade

Ujihara

et al. 1968

Japanese Journal of Microbiology

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Some single-stranded RNA's, notably RNA from E. coli bacteriophage MS2, were found to induce interference with viral growth (Sindbis, vesicular stomatitis, and vaccinia viruses) in chick embryo cell culture. Oligonucleotides appear to have a more essential role for induction of interference than high molecular weight RNA, since (a) phage RNA preparations containing degraded components are more consistently effective than preparations consisting essentially of intact molecules, (b) chick embryo RNA (homologous to the cells), ineffective in itself, becomes strongly effective after digestion with T1 RNase, and (c) calf liver RNA, which gives variable results, becomes reproducibly effective after T1 RNase digestion. Certain structural specificities of oligonucleotides are required, since (a) digests by pancreatic RNase, (b) Ti RNase digests of E. coli and yeast RNA's, and (c) mononucleotides, are all ineffective or only slightly effective. Various characteristics of the interference observed indicate that the RNA does not directly inactivate free virus but inhibits viral replication, most probably by inducing some cellular processes unfavorable for viral growth. Release of interferon into the culture medium during or after RNA treatment was examined, but in many cases only low titers or none of interferon activity were observed. Experiments on Newcastle disease virus, a virus relatively insensitive to interferon, yielded variable results as to its sensitivity to RNA-induced interference. Thus the role of interferon in the RNA-induced interference described here remains unsettled.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Interference with Virus Infection Induced by RNA in Chick Embryo Cells

Fukada

Kawade

Ujihara

et al. 1968

Japanese Journal of Microbiology

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“…The cancer cell-intrinsic effectiveness of Type-I-IFNs is well documented in experimental animal systems and is reported to depend on specific cellular effects such as growth inhibition, 47 modulation of apoptosis, 48 differentiation, 49 migration, 49 alteration of cell surface expression of TAAs 50 and promotion of the epithelial-to-mesenchymal transition (EMT). 51 Type-IIFNs are known to affect different phases of the mitotic cellcycle (panel 1, Fig.…”

Section: Cancer-intrinsic Effects Of Type-i-ifnsmentioning

confidence: 99%

Type-I-interferons in infection and cancer: Unanticipated dynamics with therapeutic implications

et al. 2017

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If there is a great new hope in the treatment of cancer, the immune system is it. Innate and adaptive immunity either promote or attenuate tumorigenesis and so can have opposing effects on the therapeutic outcome. Originally described as potent antivirals, Type-I interferons (IFNs) were quickly recognized as central coordinators of tumor-immune system interactions. Type-I-IFNs are produced by, and act on, both tumor and immune cells being either host-protecting or tumor-promoting. Here, we discuss Type-I-IFNs in infectious and cancer diseases highlighting their dichotomous role and raising the importance to deeply understand the underlying mechanisms so to reshape the way we can exploit Type-I-IFNs therapeutically.

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“…However, the immunostimulatory activity of nucleic acids had long been recognized. Already in 1963, two separate groups reported the observation that DNA and RNA derived from pathogens or host cells were capable of inducing interferon (IFN) production in fibroblasts (156,309), but cellular receptors for nucleic acids, as well as for other microbial components, have remained unknown until a few years ago (12,76,119,121,243,357,393). Accordingly, the current view on pathogen recognition has been shaped only during the last two decades, initiated by Janeway's hypothesis and further stimulated by the identification of TLRs in 1997 (154,243).…”

Section: Introductionmentioning

confidence: 99%

Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses

2009

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SUMMARY The innate immune system constitutes the first line of defense against invading microbial pathogens and relies on a large family of pattern recognition receptors (PRRs), which detect distinct evolutionarily conserved structures on pathogens, termed pathogen-associated molecular patterns (PAMPs). Among the PRRs, the Toll-like receptors have been studied most extensively. Upon PAMP engagement, PRRs trigger intracellular signaling cascades ultimately culminating in the expression of a variety of proinflammatory molecules, which together orchestrate the early host response to infection, and also is a prerequisite for the subsequent activation and shaping of adaptive immunity. In order to avoid immunopathology, this system is tightly regulated by a number of endogenous molecules that limit the magnitude and duration of the inflammatory response. Moreover, pathogenic microbes have developed sophisticated molecular strategies to subvert host defenses by interfering with molecules involved in inflammatory signaling. This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response. Moreover, medical implications are discussed, including the role of PRRs in primary immunodeficiencies and in the pathogenesis of infectious and autoimmune diseases, as well as the possibilities for translation into clinical and therapeutic applications.

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Interferon Responses of Chick Embryo Fibroblasts to Nucleic Acids and Related Compounds

Cited by 64 publications

References 2 publications

Interference with Virus Infection Induced by RNA in Chick Embryo Cells

Interference with Virus Infection Induced by RNA in Chick Embryo Cells

Type-I-interferons in infection and cancer: Unanticipated dynamics with therapeutic implications

Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses

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