Disease relevance of IFNA

• Southern blot analysis and screening of a genomic lambda phage library with the previously cloned chicken interferon (IFN) cDNA indicated that the chicken genome contains at least 10 IFN genes [1].
• Selective defect of natural killer and killer cell activity against lymphomas in SJL mice: low responsiveness to interferon inducers [2].
• RNA methylation in vaccinia virus-infected chick embryo fibroblasts treated with homologous interferon [3].
• Newcastle disease virus V protein is associated with viral pathogenesis and functions as an alpha interferon antagonist [4].
• Interferon induction by adenovirus type 12: stimulatory function of early region 1A [5].

High impact information on IFNA

• Interferon-induced nuclear signalling by Jak protein tyrosine kinases [6].
• Suramin, pentosan polysulfate, and interferon alpha, which are currently in use for therapy of KS, were either less effective than SP-PG or much more cytotoxic, or both [7].
• Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-gamma secretion by natural killer (NK) cells [8].
• Interferon-induced differentiation of U937 cells. Comparison with other agents that promote differentiation of human myeloid or monocytelike cell lines [9].
• BACKGROUND & AIMS: Previous data suggest that oral antigen induces interferon (IFN)-gamma production in intestinal T cells [10].

Chemical compound and disease context of IFNA

• Mice reconstituted with AKR bone marrow were deficient both in interferon production using tilorone and Newcastle disease virus as inducers, and at the level of natural killer cells responding to exogenously administered interferon [11].
• Addition of 2-aminopurine to an agarose overlay resulted in high efficiency plaque formation by vesicular stomatitis virus New Jersey (Hazelhurst) under conditions where endogenous induction of interferon and its feedback action on aged chick embryo cells normally prevented plaque formation [12].
• Hydroxylamine treatment of virion-extracted RNA and neutralization of intact virions by antibody abolished the capacity of the virus to induce interferon [13].
• SVMPA, a mutant of sindbis virus resistant to mycophenolic acid and ribavirin, shows an increased sensitivity to chick interferon [14].
• The combined effect of interferon and 5-FU on tumor-cell metastasis in the nude mouse [15].

Biological context of IFNA

• It is intriguing that the smallest of the three introns is located just in the middle of the Glu-Glu sequence which is conserved among all three forms of interferon at approximately the same position [16].
• In principle, divergent views of interferon action may be reconciled to a common mode of action by postulating that viral interference results from a newly induced or activated RNase of cellular origin and proper specificity that acts to reduce the accumulation and functional capacity of newly synthesized viral RNAs, particularly mRNA [17].
• The promoter region is particularly G+C-rich and contains, in addition to interferon regulatory elements, potential S/W, X, and Y boxes that were originally described for mammalian class II but not class I alpha or beta 2-microglobulin genes [18].
• To examine this response in greater detail, we studied its kinetics under the following conditions: (i) cessation of interferon treatment after different lengths of time, (ii) delayed inhibition of RNA or protein synthesis, and (iii) combinations of these treatments [19].
• IRF-10 binds the interferon-stimulated response element site of the MHC class I promoter [20].

Anatomical context of IFNA

• DNA from these clones specified biologically active interferon upon injection into the nuclei of Xenopus laevis oocytes [16].
• Oligonucleotide inhibitor of protein synthesis made in extracts of interferon-treated chick embryo cells: comparison with the mouse low molecular weight inhibitor [21].
• Because interferon can alter the program of events involved in conversion of 3T3-L1 fibroblasts into adipose cells, it may be able to affect the regulation of eukaryotic cell differentiation [22].
• Variously inactivated or mock interferon preparations as well as interferons from several heterologous species fail to inhibit 3T3-L1 adipocyte conversion [22].
• Murine natural killer (NK) cell activity against lymphoma targets can be classified into three major functional phenotypes, i.e., low, inducible, and high, according to the levels of endogeneous activity and the extent of augmentation by interferon (IFN) or IFN inducers, as previously described [23].

Associations of IFNA with chemical compounds

• Induction and maintenance of 2',5'-oligoadenylate synthetase in interferon-treated chicken embryo cells [19].
• Virus and interferon effects on cellular prostaglandin biosynthesis [24].
• Treatment of CEF culture, prepared from 11-day-old embryos, with recombinant chicken gamma interferon (rChIFN-gamma) and lipopolysaccharide (LPS) resulted in production of NO which was suppressed by the addition of N(G)-monomethyl L-arginine (NMMA), an inhibitor of inducible NO synthase (iNOS) [25].
• The mechanism of inhibition may involve a direct effect of Cy A on "induced" or "activated" NK cells or inhibition of the release of Poly IC-induced interferon from lymphocytes [26].
• Two other inducible systems, representing genes involved in interferon action (both its development and activation), and those of heat shock, were not affected by 2-aminopurine [12].

Enzymatic interactions of IFNA

• Vinculin and 36 kDa protein are not tyrosine-phosphorylated in Rous sarcoma virus infected cells which have been treated with interferon [27].

Regulatory relationships of IFNA

• The interferon-induced Mx protein of chickens lacks antiviral activity [28].
• Interferon suppresses glutamine synthetase induction in chick embryonic neural retina [29].

Other interactions of IFNA

• The expression of IRF-4 antisense RNA eliminated formation of soft agar colonies by v-Rel and reduced the proliferation of v-Rel-transformed cells. v-Rel-transformed fibroblasts produced interferon 1 (IFN1), which inhibits fibroblast proliferation [30].
• Genomic DNA containing the first four exons and upstream sequences of the interferon (IFN)-inducible chicken Mx gene was cloned and sequenced [31].
• Low GBP RNA levels were found in cells treated with type I interferon, whereas very high levels were observed in cells treated with supernatant of a chicken T cell line that secretes a gamma-interferon-like activity [32].
• To gain further insights into the cytokine network of birds, we used polymerase chain reaction technology to clone a cDNA that codes for a chicken homolog of the interferon-induced guanylate-binding proteins (GBPs) [32].
• Gamma interferon (IFN-gamma) mRNA was expressed by splenocytes from all infected birds between 3 and 10 dpi, associated with increasing MDV loads [33].

Analytical, diagnostic and therapeutic context of IFNA

• This incorporation is a sensitive bioassay of the antidifferentiation effect of interferon; less than 1 antiviral unit is inhibitory [22].
• Inhibition was maximum at 24 h after treatment with 1,000 U of interferon per ml and was dose dependent and reversible with time [34].
• Use of chicken cell line LSCC-H32 for titration of animal viruses and exogenous chicken interferon [35].
• Northern blot analysis revealed strong degradation of residual TK mRNA prepared from interferon-treated chick embryo fibroblasts (CEF) [36].
• Characterization of viral mutants obtained after site-directed mutagenesis indicated that the same mutations responsible for the host restriction of SVMPA in secondary cultures of CEF were also responsible for its increased sensitivity to chick interferon [14].

References