Biochemistry of Interferons and Their Actions

Lengyel, Péter

doi:10.1146/annurev.bi.51.070182.001343

Cited by 842 publications

(332 citation statements)

References 118 publications

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“…It activates an endonuclease at nM levels. This endonuclease-mediated degradation of RNA has been suggested as a mechanism by which interferon exerts its anticellular and antiviral effects [1,2]. However, a direct evaluation of anticellular or antiviral effect of 2-SA has not been possible because of its polar nature which makes it impermeable to most cells.…”

Section: Introductionmentioning

confidence: 99%

“…Although the 2-SA core is inactive in vitro [ 1,2,10,11], in intact cells, it produces inhibition of protein synthesis, although at much higher concentrations. This is presumably because in intact cells, kinases are thought to exist that introduce the 5 '-triphosphate group in the 2-SA core mo@cule, although this has never been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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3′‐O‐Methylated analogs of 2–5A as inhibitors of virus replication

et al. 1983

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We. have explored analogs of 2 ' -5 t-linked andeylic acid trimer (2-5A): 3 ' Gmethylated 2-5A, 2 '-end modified adenylate trimer with deoxyadenosine or araadenine, methyl phosphonate and methyl phosphorotriester analogs as potential antiviral agents. For the treatment of virus infections, 2-5A and its analogs may serve in lieu of interferon, however, the use of 2-SA has two serious limitations: it is presumed to be impermeable to most cells, and moreover, celluhu enzymes rapidIy degrade it. Methylated analogs of 2-5A core strongly inhibited virus growth when added directly to cells in culture. 2'-End modified adenylate trimer with araadenine also inhibited virus growth, however, neither 2-5A nor other analogs showed any significant antiviral activity. The inhibition of virus growth was not due to the toxic effect of these compounds on cell growth as they had no inhibitory effect on the growth of uninfected cells

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

3′‐O‐Methylated analogs of 2–5A as inhibitors of virus replication

et al. 1983

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“…It is well known that IFN-b has many biological effects. 42,43 IFN-b exhibits antitumor effects via various mechanisms, such as upregulation of MHC class I, 44 activation of macrophages and NK cells, 45 downregulation of angiogenic agents 46 and inhibition of tumor cell proliferation. 47 It is likely that inhibition of tumor cell proliferation by IFN-b is one of the most important mechanisms in our study, because the cell growth inhibitory effect of IFN-b was often higher than that of IFN-a and g 47,48 and, in fact, the in vitro growth of CT-26 cells was efficiently inhibited by IFN-b.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of intravenous delivery of lipoplexes containing the interferon-β gene and poly I: poly C in a murine lung metastasis model

et al. 2003

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We have evaluated and compared the efficacy of systemic administration of lipoplex formulations containing plasmids encoding IFN-b or IFN-g, and a synthetic double-strand RNA poly I:poly C (pI:pC), a type I IFN inducer, in a lung metastasis model in which colon carcinoma CT-26 cells were inoculated intravenously into immunocompatible mice. Injection of lipoplexes containing plasmid DNA, regardless of IFN gene insertion, stimulated a transient increase in the serum concentration of proinflammatory cytokines such as tumor necrosis factor (TNF)-a and IFN-g, while injection of lipoplexes containing pI:pC led to a low level of TNF-a and undetectable IFN-g production. Furthermore, injection of these lipoplexes containing plasmids resulted in the production of a mixture of type I and type II IFNs, partly derived from the inserted IFN genes, in lung tissue cultures. In tumor-prophylactic experiments, intravenous injection of lipoplexes containing plasmid, regardless of IFN gene insertion, showed a significant reduction in lung metastatic nodules probably due to proinflammatory cytokines such as TNF-a and IFN-g nonspecifically induced by the CpG motifs in the plasmid and the type I IFNs produced. On the other hand, the antimetastatic effect of pI:pC-lipoplex seemed to be due mainly to IFN-b induced by pI:pC. In established lung metastasis experiments, a single intravenous administration of lipoplexes containing IFN-b gene or pI:pC, but not other lipoplexes, showed a significant therapeutic effect on the tumor metastasis: reduction in tumor nodules and prolongation of survival time of tumor-burden mice. The therapeutic effects were specifically impaired by anti-IFN-b antibody treatment, indicating that IFN-b produced by the lipoplexes played an important role in the suppression of established metastatic lung tumors. Thus, the local IFN-b in the lung delivered by intravenous administration of lipoplex containing IFN-b gene or pI:pC may be a convenient and useful method of inhibiting established metastatic lung tumors.

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“…Interferon has attracted a great deal of attention, not only because of its antiviral effect, but also because of its other biological activities [ 1,2]. It is not a single protein but refers to a large family of proteins varying from species to species and present in multiple forms even within a single species [2].…”

Section: Introductionmentioning

confidence: 99%

“…It is not a single protein but refers to a large family of proteins varying from species to species and present in multiple forms even within a single species [2]. These classes have been defined for human interferon and have been designated as leukocyte interferon (cu), fibroblast interferon GB) and immune interferon (7).…”

Section: Introductionmentioning

confidence: 99%

Prediction structure type for human leukocyte Interferon subtype A from circular dichroism

Manavalan¹,

Johnson²,

Johnston³

1984

FEBS Letters

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Vacuum UV circular dichroism studies were carried out on human leukocyte interferon subtype A. The secondary structure analysis for the CD spectrum shows 59% a-helix, 16% antiparallel p-sheet, no parallel p-sheet, 18% j-turns and 13% other structures. The analysis of the CD features for the prediction of tertiary structural class reveals that it is an all-a type protein. Circular dichroismProtein secondary structure Interferon Tertiary fold

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Biochemistry of Interferons and Their Actions

Cited by 842 publications

References 118 publications

3′‐O‐Methylated analogs of 2–5A as inhibitors of virus replication

3′‐O‐Methylated analogs of 2–5A as inhibitors of virus replication

Therapeutic effect of intravenous delivery of lipoplexes containing the interferon-β gene and poly I: poly C in a murine lung metastasis model

Prediction structure type for human leukocyte Interferon subtype A from circular dichroism

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