Disease relevance of IFNA1

• Transmissible gastroenteritis virus, an enteropathogenic coronavirus of swine, is a potent inducer of alpha interferon (IFN-alpha) both in vitro and in vivo [1].
• Overall, these data supported the view that an interferogenic determinant resides in the N-terminal, exposed part of the molecule and provided further evidence for the direct role of M protein in the induction of IFN-alpha by transmissible gastroenteritis virus [1].
• We previously demonstrated that the ability of foot-and-mouth disease virus (FMDV) to form plaques in cell culture is associated with the suppression of alpha/beta interferon (IFN-alpha/beta) [2].
• BACKGROUND: Interferon alpha-2b (IFNalpha) treatment of diseases can be accompanied by impaired renal function and capillary leak syndrome [3].
• NIPC isolated from pigs immunised against classical swine fever virus (CSFV), a member of the Flaviviridae, were more receptive to viral infection and produced higher levels of IFN-alpha than NIPC from immunologically naive animals [4].

High impact information on IFNA1

• Here we show that in addition to preventing IFN-alpha/beta protein synthesis, L(pro) reduces the level of immediate-early induction of IFN-beta mRNA and IFN-stimulated gene products such as double-stranded RNA-dependent protein kinase R (PKR), 2',5'-oligoadenylate synthetase, and Mx1 mRNAs in swine cells [5].
• Previously, we showed that ncp BVDV inhibits the induction of apoptosis and alpha/beta interferon (IFN-alpha/beta) synthesis by double-stranded RNA (dsRNA) [6].
• The attenuated phenotype apparently is a consequence of the inability of A12-LLV2 to block the expression of type I interferon (IFN-alpha/beta) protein, resulting in IFN-induced inhibition of FMDV replication [5].
• The absence of IFN-alpha in Pr4-infected macrophages suggests that MGF360/530 genes either directly or indirectly suppress a type I IFN response [7].
• The antiviral activity in supernatants from A12-LLV2-infected embryonic bovine kidney cells is IFN-alpha/beta specific, as assayed with mouse embryonic fibroblast cells with or without IFN-alpha/beta receptors [8].

Chemical compound and disease context of IFNA1

• The DC produced the Th1 associated cytokines IFN-alpha at Sendai virus stimulation, and IL-12 at stimulation with plasmid DNA (pre-incubated in the presence of lipofectin), heat-inactivated Actinobacillus pleuropneumoniae, UV-inactivated Aujeszky's disease virus and live Sendai virus [9].
• The in vitro ability of peripheral blood mononuclear leukocytes (PBMCs) to produce IFN-alpha after stimulation by glutaraldehyde-fixed pseudorabies virus-infected PK15 cells and their proliferative response to the T-cell mitogen leukoagglutinin (LA) was also monitored [10].
• Arenavirus infection in the guinea pig model: antiviral therapy with recombinant interferon-alpha, the immunomodulator CL246,738 and ribavirin [11].

Biological context of IFNA1

• Mapping of the porcine alpha interferon (IFNA) gene to chromosome 1 by fluorescence in situ hybridization [12].
• DC activation was monitored in terms of MHC class II and CD80/86 upregulation, as well as the production of type I interferon (IFN-alpha/beta) [13].
• Recombinant plasmids for intracellular synthesis of mature porcine interferon alpha 1 (IFN-alpha 1) in Escherichia coli were constructed [14].
• Nucleotide and amino acid sequence comparisons establish that oTP shares extensive homology with alpha-interferon (IFN-alpha) but is more closely related to the IFN-alpha sII subfamily [15].
• Identification of a sequence from the genome of porcine circovirus type 2 with an inhibitory effect on IFN-alpha production by porcine PBMCs [16].

Anatomical context of IFNA1

• Using as a probe pig genomic DNA, including the complete interferon alpha gene, we have mapped the leukocyte interferon gene on pig chromosome 1 by in situ hybridization [17].
• Previous studies have shown that virus-infected fixed cells or viral suspensions were able to induce an early and strong IFN-alpha synthesis by naive lymphocytes [1].
• Natural interferon-producing cells (NIPC), also called plasmacytoid dendritic cells, are the most potent producers of IFN-alpha in response to viral and bacterial components, serving an important function in innate immune defences [4].
• CONCLUSIONS: These findings provide evidence that IFNalpha can directly affect barrier function in renal epithelial cells [3].
• Using double immunohistochemical labelling for both IFN-alpha and leukocyte markers, we established that splenic NIP cells were not T or B cells [18].

Associations of IFNA1 with chemical compounds

• Tyrphostin, an inhibitor of phosphotyrosine kinases, ameliorated the IFNalpha-induced decrease in TER [3].
• Recombinant porcine IFN-alpha 1 (rIFN-alpha 1) was purified to homogeneity by monoclonal antibody immunoaffinity and was found to have the expected Mr (17.5K) and N-terminal sequence (except for the apparent lack of an N-terminal methionine) [14].
• Stimulation of DCs with IFN-alpha/TNF-alpha or polyinosinic-polycytidylic acid (pIC) induced phenotypic maturation with increased MHC and CD80/86 expression, both with mock-treated and infected DCs [19].
• Interestingly, also A. pleuropneumoniae induced a substantial production of IFN-alpha when preincubated with lipofectin [20].
• Con A pretreatment of TGEV-infected cell monolayers before fixation with glutaraldehyde and exposure to PBMC caused a dose-dependent inhibition of IFN alpha induction, implying that masking of carbohydrates at the surface of infected cells lowered IFN-alpha-induction [21].

Regulatory relationships of IFNA1

• The treatment with IFN-alpha induced the expression of PKR 3.9-fold in a porcine kidney cell line, LLC-PK1 [22].

Other interactions of IFNA1

• Interestingly, 8% of tonsil pDC and 15% of blood pDC were shown to secrete IFN-alpha, while 18-20% of cDC expressed TNF-alpha in these tissues [23].
• Levels of serum IFN-alpha, IL-6, IL-10, and CRP were examined for a 35-day period in 10 piglets experimentally infected with PCV2 at 3 weeks of age [24].
• A bioassay was used to detect IL-6 and ELISAs were used to detect IFN-alpha, IL-10, and CRP [24].
• To determine if suppression was at the level of IFN-alpha transcription, quantitative RT-PCR was performed for IFN-alpha mRNA and compared to GAPDH and cyclophilin mRNA quantification [25].
• Immunofluorescence confocal microscopy revealed a broader staining of occludin and E-cadherin following IFNalpha treatment, with prominent staining at the basal cell pole in addition to localization at the junctional region [3].

Analytical, diagnostic and therapeutic context of IFNA1

• The results obtained with cell cultures demonstrate that the ability of A12-IC to form plaques is associated with the suppression of IFN-alpha/beta expression and suggest a role for this host factor in the inability of A12-LLV2 to spread and cause disease in susceptible animals [8].
• Stimulation of NIPC with such immune complexes employs FcgammaRII ligation, leading to strong secretion of IFN-alpha [26].
• Increased expression of occludin and E-cadherin was detected by Western blot analysis after IFNalpha treatment [3].
• In this study, NIP cells were analysed in vivo after an intravenous injection of UV-inactivated transmissible gastroenteritis virus in newborn piglets, which resulted in strong serum IFN-alpha production [18].
• A striking finding was that IFN-alpha SC could be detected in the fetal liver as early as at 26 days of gestation, i.e., during the first quarter of gestation, a period at which T-cell markers could not be detected by flow cytometry [27].

References