Disease relevance of IFN-a

• Ovine trophoblast protein 1 (oTP-1) is the interferon alpha (IFN-alpha) variant with potent antiviral activity and low toxicity that is responsible for maternal recognition of pregnancy in sheep [1].
• Retinoic acid and interferon alpha act synergistically as antiangiogenic and antitumor agents against human head and neck squamous cell carcinoma [2].
• Vaccinia virus B18R gene encodes a type I interferon-binding protein that blocks interferon alpha transmembrane signaling [3].
• Among the antiviral proteins that are synthesized in response to interferon-alpha/beta stimulation, Mx proteins from several species are long known to block the replication of vesicular stomatitis virus (VSV) [4].
• Expression of the interferon-alpha/beta-inducible bovine Mx1 dynamin interferes with replication of rabies virus [4].

High impact information on IFN-a

• Signal transduction pathways in the induction of 2',5'-oligoadenylate synthetase gene expression by interferon alpha/beta [5].
• Treatment of quiescent BALB/c mouse 3T3 cells with murine interferon alpha/beta (IFN-alpha/beta) (1000 units/ml) leads to the appearance at 4 hr of 1.7-kilobase 2',5'-oligoadenylate (2',5'-OAS)mRNA as detected by Northern blot analysis [5].
• Retinoic acid (RA) and interferon alpha (IFN-alpha), drugs with known biological activity against HNSCC when used individually, are also inhibitors of angiogenesis [2].
• The combination of RA and IFN-alpha also acted synergistically on endothelial cells by reducing their responsiveness to both interleukin-8 and tumor conditioned media [2].
• Importantly, the combination of these agents with interferon-alpha results in synergistic inhibition of HCV genome replication in cell culture [6].

Chemical compound and disease context of IFN-a

• Possible mechanisms for reduction of circulating concentrations of progesterone by interferon-alpha in cows: effects on hyperthermia, luteal cells, metabolism of progesterone and secretion of LH [7].
• Current standard therapy for the treatment of chronic infections with hepatitis C virus consists of combination therapy with (pegylated) interferon-alpha and ribavirin [8].
• Effect of levamisole and bovine interferon alpha 1 on bovine immune responses and susceptibility to bovine herpesvirus-1 [9].
• The induction of interferon-alpha (IFN-alpha) and IFN-beta mRNA in natural IFN producing (NIP) cells in cultures of human peripheral blood mononuclear cells (PBMCs), stimulated by glutaraldehyde-fixed Herpes simplex virus type 1 (HSV)-infected WISH cells, was studied [10].

Biological context of IFN-a

• The bovine genome contains a gene family of interferon-alpha s (bIFN-alpha) that consists of at least five distinct members [11].
• Compared with the published BoIFN-a subtypes, the IFN-a gene of Holstein cow had only one point mutation with the BoIFN-aA subtype [12].
• The amino-terminal amino acid sequences were similar among the components as well as to those reported for the cloned human IFN-alpha genes (Pestka, S. (1986) Methods Enzymol. 119, 3-14) [13].
• Twenty-two components of human interferon-alpha (IFN-alpha) derived from Sendai virus-induced Namalwa cells were purified by sequential immunoadsorbent affinity chromatography using four monoclonal antibody affinity columns followed by ultrafiltration and reversed-phase high-performance liquid chromatography [13].
• In this study, we demonstrate that ncp BVDV inhibits the induction of apoptosis and the expression of interferon alpha/beta by poly(IC), a synthetic double-stranded RNA (dsRNA) [14].

Anatomical context of IFN-a

• Antiviral activity assays showed that the six recombinant IFN-a (rIFN-a) all exhibited 1000 times higher antiviral activity in the MDBK/VSV cell line than in the CEF/VSV one [12].
• Interferon-tau and interferon-alpha interact with the same receptors in bovine endometrium. Use of a readily iodinatable form of recombinant interferon-tau for binding studies [15].
• Reconstitution of virus-mediated expression of interferon alpha genes in human fibroblast cells by ectopic interferon regulatory factor-7 [16].
• Together, these results demonstrate that ACs can provide help to NK cells in both IFN-alpha-dependent and -independent manners [17].
• The infusion of recombinant bovine interferon-alpha I 1 into the uterus of cyclic cows from day 15.5 to 21 after estrus delayed luteolysis [18].

Associations of IFN-a with chemical compounds

• Down-regulation of the noradrenaline transporter by interferon-alpha in cultured bovine adrenal medullary cells [19].
• In contrast, when the arginine analogue canavanine was added to NK assays, no IFN-alpha was produced and NK(HSV-Fs) activity was only partially inhibited [17].
• The effect of tunicamycin on interferon-alpha production in a human lymphoblastoid cell line (Namalwa) [20].
• A series of experiements was performed to determine whether proteins produced by the sheep conceptus (oCSP) during the time of maternal recognition of pregnancy or bovine recombinant interferon alpha 1-1 (brIFN) decrease oxytocin receptor concentrations in the endometrium of cyclic or ovariectomized progesterone-treated ewes [21].
• Alteration of oestrous cycle length, ovarian function and oxytocin-induced release of prostaglandin F-2 alpha by intrauterine and intramuscular administration of recombinant bovine interferon-alpha to cows [22].

Other interactions of IFN-a

• BAM cells treated with bovine interferon-alpha and then stimulated with P. haemolytica produced higher amounts of IL-1, IL-8 and TNF-alpha proteins compared to BAM stimulated with P. haemolytica alone [23].
• Bovine interferon-alpha I1 (IFN-alpha I1) and porcine interferon-gamma (IFN-gamma) inhibited African swine fever virus replication in both porcine monocytes and alveolar macrophages [24].
• Stimulation of 2',5'-oligoadenylate synthetase activity in sheep endometrium during pregnancy, by intrauterine infusion of ovine trophoblast protein-1, and by intramuscular administration of recombinant bovine interferon-alpha I1 [25].
• The aim of the present study was to determine whether bTP-1 inhibits proliferation of lymphocytes induced by mitogens, mixed lymphocyte cultures (MLC) and interleukin-2 (IL-2) and, if so, whether this activity is similar to that of a related interferon, bovine interferon-alpha I1 (bIFN-alpha I1) [26].
• Intrauterine infusion of 1 mg of recombinant bovine interferon-alpha I1, twice daily, to lactating dairy cows from d 14 to 21 after estrus extended interestrous interval (30.4 +/- 1.91 d versus 24.8 +/- .58 d) and functional lifespan of the corpus luteum (28.4 +/- 2.01 d versus 23.6 +/- .75 d) [27].

Analytical, diagnostic and therapeutic context of IFN-a

• Sequence analysis showed that IFN-a genes of six clones were composed of 498 nucleotides, encoding a mature polypeptide with 166 amino acids [12].
• A highly significant difference was evident in the chi 2 test when PCR was compared with specific antigen detection or antibody evaluation (n = 19; chi 2 = 7; sensitivity = 100% vs. 63%) or with interferon alpha determination (n = 20; chi 2 = 11; sensitivity = 95% vs. 42%) [28].
• Induction of the synthesis of the pregnancy-specific protein p70 in the endometrium by intramuscular injection of recombinant bovine interferon-alpha I1 in nonpregnant ewes [29].
• Gelatin microspheres (ms) and gelatin/BSA (bovine serum albumin) or gelatin/alginate ms were prepared by encapsulating fluorescein isothiocyanate (FITC) labeled dextran or interferon alpha (IFN-alpha) [30].
• Preparation and evaluation of once-a-day injectable microspheres of interferon alpha in rats [30].

References