Disease relevance of IFNB1

• A region of chromosome 9, surrounding the interferon-beta (IFNB1) locus and the interferon-alpha (IFNA) gene cluster on 9p13-p22, has been shown to be frequently deleted or rearranged in a number of human cancers, including leukemia, glioma, non-small-cell lung carcinoma, and melanoma [1].
• Moreover, mouse asialo-IFN-beta profoundly reduced viremia in vivo in HBV-transfected athymic nude mice, in contrast to conventional IFN-beta, which had no substantial effect [2].
• In dose response studies, pretreatment with approximately 100 U/ml of IFN-alpha, approximately 10 U/ml of IFN-beta, or approximately 100 U/ml of IFN-gamma was sufficient to prevent virion release maximally and to prevent cytopathology completely [3].
• As the result of PKR loss, they also showed impaired induction of IFN-alpha and IFN-beta genes in response to several inducers--specifically, encephalomyocarditis virus, lipopolysaccharide, and phorbol 12-myristate 13-acetate [4].
• Homozygous and hemizygous deletions of the interferon A (IFNA) and IFNB genes have been frequently observed in acute leukemia cell lines, primary acute leukemia cases, and gliomas [5].

Psychiatry related information on IFNB1

• Deletion of the RIG-I RD resulted in constitutive signaling to the IFN-beta promoter, whereas RD expression alone prevented signaling and increased cellular permissiveness to HCV [6].
• Detection of RNA molecules occurs during viral infection and triggers antiviral innate defense mechanisms including the induction of type I interferons (IFN-alpha, IFN-beta) and downregulation of gene expression [7].
• The neurotoxicity of interferon-beta (IFN-beta) was assessed by performing electrophysiological examinations and neuropsychological tests on 22 patients with malignant hematological diseases before, during, and after IFN-beta treatment [8].
• QoL during treatment with IFN-beta is influenced by depressive symptoms at baseline as well as by treatment-associated side-effects [9].

High impact information on IFNB1

• Type I interferon (IFN-alpha and IFN-beta) is secreted by virus-infected cells [10].
• Conversely, overexpression of MAVS induces the expression of IFN-beta through activation of NF-kappaB and IRF 3, thus boosting antiviral immunity [11].
• We show that delivery of this nucleosome to the same downstream position to create an accessible IFN-beta core promoter prior to enhanceosome assembly results in major changes in the gene expression program with regard to the temporal pattern and the signal specificity of the transcriptional response [12].
• Transcriptional activation of the IFN-beta gene in response to virus infection requires the assembly of an enhanceosome, which instructs a recruitment program of chromatin modifiers/remodelers and general transcription factors to the promoter [12].
• Here, we show that a nucleosome obstructing transcription from the IFN-beta promoter slides in vivo in response to virus infection, thus exposing the previously masked TATA box and the initiation site, a requirement for transcriptional activation [13].

Chemical compound and disease context of IFNB1

• Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a critical mediator of IFN-beta-induced apoptosis, but most melanoma cell lines were resistant to recombinant TRAIL protein [14].
• In contrast, both IFN-alpha and IFN-beta exerted some inhibitory effect on HIV production, which was more marked in vitamin D3-treated cultures than in untreated cultures [15].
• The molecular basis for the enhanced growth inhibition of MCF-7 human breast cancer xenografts by a combination of human interferon-beta (IFN-beta) and tamoxifen was investigated [16].
• Poly I:C was not able to induce melanocytes or melanoma cells to produce detectable amounts of IFN-alpha protein, but able to induce a significant amount of IFN-beta in melanocytes and two of the melanoma cell lines: MMAc and VMRC-MELG [17].
• A human transient expression system was used to measure the influence of simian virus 40 T antigen and adenovirus E1a proteins on the activation of alpha interferon subtype 1 (IFN-alpha 1) and IFN-beta promoters linked to the reporter chloramphenicol acetyltransferase gene [18].

Biological context of IFNB1

• All three mapping approaches gave concordant results and, in the case of multipoint linkage analysis, the following gene order was supported for these and other closely linked chromosome 9 markers present in the CEPH database: pter-D9S33-IFNB1/IFNA-D9S126-D9S3-D9S19 -D9S9/D9S15-ASSP3-qter [1].
• The ratio of beta-PTyr to IFNAR tyrosine phosphorylation is much higher with IFN-beta than with IFN-alpha 2 or 8 [19].
• ISG15 is a 15-kDa protein of unique primary amino acid sequence, which is transcriptionally regulated by interferon (IFN) alpha and IFN-beta [20].
• Earlier we demonstrated that beta interferon (IFN-beta) can inhibit tumor necrosis factor (TNF)-induced IL-8 gene expression at the transcriptional level, apparently by a novel mechanism [21].
• The cytokines tumor necrosis factor (TNF), beta interferon (IFN-beta), and IFN-gamma increase major histocompatibility complex class I molecule expression [22].

Anatomical context of IFNB1

• To define the location and extent of deletions of 9p in NSCLC and MM, Southern blot analyses on six NSCLC and five MM cell lines using molecular probes to 9p loci (IFNA, IFNB1, D9S3, and D9S19) were performed, and DNA dosage was determined by densitometry [23].
• Pretreatment with rIFN-alpha, IFN-beta, and IFN-gamma, or bacterial LPS prevented viral replication in macrophages [3].
• Here we purify ISG15-modified proteins from IFN-beta-treated human (HeLa) cells by using double-affinity selection and use mass spectroscopy to identify a large number (158) of ISG15 target proteins [24].
• Patients with AIDS have recurrent infections and/or malignancy and altered immune response, including decreased T lymphocyte counts, decreased T helper lymphocytes, defective T cell blastogenesis, hypergammaglobulinemia, defective natural killer (NK) activity and impaired response of NK to interferon-beta (IFN-beta) [25].
• Because hemophiliacs are subjected to chronic antigen stimulation secondary to the administration of foreign protein, the reactivity of NK cells from patients with hemophilia to IFN-alpha, IFN-beta and IFN-gamma was studied [25].

Associations of IFNB1 with chemical compounds

• Furthermore, the enhanced antiviral effect of asialo-IFN-beta was supported by induction of the 2'-5' oligoadenylate synthetase, an indicator of IFN activity, at a level significantly higher than that produced by conventional IFN-beta [2].
• Because the asialoglycoprotein (ASGP) receptor is specifically expressed in the liver at high density, the ASGP receptor-binding domain was generated within an N-glycosylated human IFN-beta molecule by the removal of sialic acid to direct this cytokine to the liver [2].
• The antiviral activity induced by poly(I).poly(C) may be a direct effect of this synthetic double-stranded RNA or secondary to the low levels of IFN-beta and IFN-omega produced by infected cells [26].
• Interestingly, the inhibitory effect was much less pronounced when IFN-beta was added greater than or equal to 1 hr before TNF [27].
• The major oligosaccharide of the recombinant IFN-beta is remarkably homogeneous with respect to terminal galactose sialylation [28].

Physical interactions of IFNB1

• A mutant IP6K2 with substitutions in the putative inositol phosphate binding domain abrogates IFN-beta-induced apoptosis [29].
• Conserved nontypeable Haemophilus influenzae-derived TLR2-binding lipopeptides synergize with IFN-beta to increase cytokine production by resident murine and human alveolar macrophages [30].
• Thus, we show that the differential activities of IFN-beta are directly related to the binding affinity for IFNAR1 [31].
• The 15-mer peptide, designated SYR6, was shown to compete with IFN-beta for binding to type I IFN receptor in a concentration-dependent manner, and was shown to elicit antiviral activity on cultured cells [32].
• In this study, we demonstrate that the formation of NF-kappa B-specific complexes on the positive regulatory domain II (PRDII) precedes the onset of detectable IFN-beta transcription in Sendai virus-infected cells [33].

Enzymatic interactions of IFNB1

• Here, we show that IFN-beta sensitizes glioma cells that harbor the unmethylated MGMT promoter and are resistant to temozolomide [34].
• Here we demonstrate that gelatinase B proteolytically cleaves IFN-beta, kills its activity, and hence counteracts this cytokine as an antiviral and immunotherapeutic agent [35].
• The percentage of IFNbeta-stimulated monocytes positive for phosphorylated STAT-1 (pSTAT-1) and the number of IL2- and IL15-stimulated T cells expressing phosphorylated STAT-5 (pSTAT-5) were determined at 0 and 24 h [36].

Regulatory relationships of IFNB1

• In turn, the autocrine production of IFN-beta induces the IFN-stimulated genes that contain binding sites for activated STATs in their promoters [37].
• We previously showed that IFN beta inhibited IFN gamma-induced DRA expression at the transcriptional level [38].
• Upon infection, constitutively expressed NF-kappaB and IRF-3 are activated and likely contribute to the rapid IFN-beta expression [37].
• Once expressed, IRF-1 may further stimulate the transcription of IFN-beta [37].
• None of these anti-IFNAR1 mAbs were able to block activity of IFN-beta. mAb 4A7 binds to a domain 1-hIFNAR1-IgG but not to a domain 2-hIFNAR1-IgG, which suggests that its binding region is located in domain 1 [39].

Other interactions of IFNB1

• Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN-beta genes [40].
• Because antigenic typing of the antiviral activity of these LK and MK preparations revealed that LK contained mainly gamma interferon (IFN-gamma), and MK, primarily IFN-beta, we investigated if any of the fibroblast-inhibiting activities could be attributed to human IFN [41].
• These results suggest that IFN-beta acts downstream of CIITA mRNA accumulation, and acts in part by reducing the functional competence of CIITA for transactivating MHC class II promoters [42].
• After IFN-beta treatment for 5 min, a tyrosine-phosphorylated protein of approximately 95 kDa (beta-PTyr) is found bound to IFNAR, but can be dissociated by denaturation [19].
• The inhibitory action of IFN-beta on IL-8 mRNA accumulation was undiminished in the presence of inhibitors of protein synthesis [27].

Analytical, diagnostic and therapeutic context of IFNB1

• A comparable increase was observed after treatment with 1 U of alpha interferon (IFN-alpha) per ml or 8 U of beta interferon (IFN-beta) per ml [43].
• The kinetics of IFN-beta gene expression in A549 cells was rapid, as shown by reverse-transcriptase PCR, and IFN-beta mRNA expression levels correlated well to the kinetics of nuclear factor-kappa B transcription factor activation [44].
• These results demonstrate the feasibility and the efficacy of such IFN-beta-mediated gene therapy [45].
• We have previously shown that IFN-beta suppresses growth of human ovarian carcinoma xenografts in vivo and induces apoptosis of ovarian carcinoma cells in vitro [29].
• Analysis of the glycopeptidase F-released carbohydrates by sequential exoglycosidase treatment, methylation analysis, and fast atom bombardment-mass spectrometry revealed that 95% of the IFN-beta oligosaccharides had the following structure: (Formula: see text) [28].

References