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With many products of the interferon system having a role n numerous cell pathways involved in apoptosis and translation of proteins, these pathways are the police and the prize of viral infection. What is this conundrum The virus must defeat the cell s machinery attempting to stop the production of viral proteins, yet parts of the cellular apparatus may be required for virus multiplication. At the same time, the cell must use its pathways that regulate cell proliferation to stop viral proliferation. Viruses vary in their ability to circumvent the host interferon response. In general, DNA viruses produce less dsRNA and initially are therefore less potent inducers of IFN.10 However, viral evasion tactics exist at much more sophisticated levels. Bray established the key role of type-1 IFN in the resistance of mice to the Ebola virus infection, showing that signi cant compromise of the interferon response gave rise to disease progress resembling that in primates.11 In line with these latter observations, Harcourt et al.12 found that induction of the major histocompatibility complex class I family of genes, OAS, interleukin-6 (IL-6), PKR, interferon (IFN) regulatory factor-1, and intercellular adhesion molecule-1 (ICAM-1) by dsRNA in human umbilical vein endothelial cells was suppressed by infection with the lovirus Ebola-Zaire. Likewise, Ebola and Marburg viruses each could infect dendritic cell cultures and support exponential viral replication without releasing. Adenovirus (AV), Epstein-Barr virus (EBV), and human immunode ciency virus type 1 (HIV-1) all encode small RNA ranscripts that bind to the active site for dsRNA binding.20,45,53,54 In uenza virus NS1 protein binds directly to PKR but has also. ECC200 Encoder In VS .NET Using Barcode encoder for .Related: Creating EAN-8 VB.NET , VB.NET ISBN Generator , Print UPC-A ASP.NET





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Drawing QR Code In NET Framework Using Barcode creator for A new recently described4 IFN-l and its class II cytokine receptor system may contribute o antiviral or other defenses by a mechanism similar to, but independent of, type I IFNs Type II IFN is IFN-g, which is produced only by certain cells involved in the immune response such as natural killer (NK), cytotoxic T cells (CD8 ), and CD4 T helper 1 (Th1) cells Not produced in direct response to the presence of virus, these IFNs are secreted when an infected cell is recognized as a part of the host s acquired immune response Type I and II IFNs share no obvious structural homology and have separate cell membrane receptors2 These receptors activate signal transduction pathways, which ultimately lead to the transcription of hundreds of interferon-stimulated genes (ISGs).

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There exists an overlap in the ISGs triggered by type I and type II IFNs Type I IFNs activate the JAK/STAT signal transduction pathway by binding to the IFN-a/b receptor (IFNAR) The cytoplasmic tails of IFNAR are associated with tyrosine kinases (JAK and TYK), which phosphorylate signal transducers and activators of transcription (STAT)5 STATs are latent transcription factors that, upon phosphorylation, dimerize and form complexes with interferon response factors (IRFs) These complexes move to the nucleus and bind to interferon-stimulated regulatory elements (ISRE)6 Several genes are then transcriptionally stimulated Of these gene products, many contribute to the antiviral actions of the host immune response PKR is a double-stranded RNA (dsRNA)-dependent serine/threonine kinase In the presence of dsRNA, most likely produced from the viral genome itself or formed from its replication or convergent transcription, PKR phosphorylates the a subunit of the eukaryotic initiation factor eIF-2.

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When eIF-2a is phosphorylated, it is unable to recycle and the translation of proteins is arrested, thereby inhibiting viral reproduction Also, activation of PKR results in the phosphorylation of substrates necessary to initiate the transcription factor NF-kB Once freed from restraint, NF-kB can enter the nucleus of the cell and bind to the IFN-b promoter7 A new recently described4 IFN-l and its class II cytokine receptor system may contribute to antiviral or other defenses by a mechanism similar to, but independent of, type I IFNs Type II IFN is IFN-g, which is produced only by certain cells involved in the immune response such as natural killer (NK), cytotoxic T cells (CD8 ), and CD4 T helper 1 (Th1) cells Not produced in direct response to the presence of virus, these IFNs are secreted when an infected cell is recognized as a part of the host s acquired immune response.

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Type I and II IFNs share no obvious structural homology and have separate cell membrane receptors2 These receptors activate signal transduction pathways, which ultimately lead to the transcription of hundreds of interferon-stimulated genes (ISGs) There exists an overlap in the ISGs triggered by type I and type II IFNs Type I IFNs activate the JAK/STAT signal transduction pathway by binding to the IFN-a/b receptor (IFNAR) The cytoplasmic tails of IFNAR are associated with tyrosine kinases (JAK and TYK), which phosphorylate signal transducers and activators of transcription (STAT)5 STATs are latent transcription factors that, upon phosphorylation, dimerize and form complexes with interferon response factors (IRFs) These complexes move to the nucleus and bind to interferon-stimulated regulatory elements (ISRE)6 Several genes are then transcriptionally stimulated Of these gene products, many contribute to the antiviral actions of the host immune response PKR is a double-stranded RNA (dsRNA)-dependent serine/threonine kinase.

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In the presence of dsRNA, most likely produced from the viral genome itself or formed from its replication or convergent transcription, PKR phosphorylates the a subunit of the eukaryotic initiation factor eIF-2 When eIF-2a is phosphorylated, it is unable to recycle and the translation of proteins is arrested, thereby inhibiting viral reproduction Also, activation of PKR results in the phosphorylation of substrates necessary to initiate the transcription factor NF-kB Once freed from restraint, NF-kB can enter the nucleus of the cell and bind to the IFN-b promoter7Related: Print UPC-A Word , Excel QR Code Generation , Generate EAN-13 Word.

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In addition, although the NS deletion mutants grew to wild- type rBRSV levels in cells lacking a functional IFN-a/b system, their replication as severely inhibited in IFNcompetent cells98 These results suggested that the NS proteins block induction of IFN-a/b gene expression Wild-type human respiratory syncytial virus (HRSV) is a poor inducer of a/b interferons (IFN-a/b) In accord with the results seen with BRSV, recombinant HRSV lacking the NS1 and NS2 genes was able to induce high levels of IFN-a and IFN-b in epithelial cells and macrophages99 The two proteins can function independently or coordinately Alphaviruses including Venezuelan (VEEV), eastern (EEEV), and western equine encephalitis viruses (WEEV) are potential agents of biological warfare and terrorism and important, naturally emerging zoonotic viruses A representative virus of this group is Sindbis virus, which possesses a nonstructural protein nsP2 that is a signi cant regulator of Sindbis virus host cell interactions.

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This protein not only is a component of the replicative enzyme complex required for replication and transcription of viral RNAs but also plays a role in suppressing the antiviral response in Sindbis virus-infected cells nsP2 may act by decreasing interferon (IFN) production100,101 In another study, White and co-workers102 found that a single change (G to A) at nucleotide 3 of the 50 untranslated region (UTR) of the Venezuelan equine encephalitis virus (VEEV) V3000 virulent strain genome resulted in a virus that was avirulent in mice This mutant showed no growth disadvantage compared to the wild-type virus in cells derived from IFN-a/bR( / )mice Induction of IFN-a/b was the same for avirulent and virulent viruses; however, the avirulent mutant virus was more sensitive than the virulent strain to the antiviral actions of IFN-a/b Thus, increased sensitivity to IFN-a/b must play a major role in the in vivo attenuation.

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