The interferon response circuit: Induction and suppression by pathogenic viruses

Haller, Otto; Kochs, Georg; Weber, Friedemann

doi:10.1016/j.virol.2005.09.024

Cited by 601 publications

(594 citation statements)

References 186 publications

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“…Induction of IFN-␣␤ occurs after TLRs, the retinoic acidinducible gene I (RIG-I), or the melanoma differentiation-associated gene 5 (MDA-5) bind dsRNA or ssRNA, leading to the activation of IFN-regulatory factors 3 and 7 (IRF-3 and IRF-7), NF-B, and AP-1 (35)(36)(37). Secreted IFN-␣␤ binding to the IFN-␣ receptor activates ISG factor 3 (ISGF3), which binds the ISRE (3,24,35).…”

Section: Discussionmentioning

confidence: 99%

Interferon-Induced Expression of MxA in the Respiratory Tract of Rhesus Macaques Is Suppressed by Influenza Virus Replication

Carroll

Matzinger

Genescà

et al. 2008

The Journal of Immunology

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To determine the relationship between influenza A virus replication and innate antiviral immune responses, rhesus monkeys were given oseltamivir before influenza A/Memphis/7/01 (H1N1) challenge. We found that oseltamivir treatment significantly reduced viral replication in the trachea (p < 0.029). Further, in the trachea of both treated and untreated monkeys the mRNA levels of most innate antiviral molecules in the IFN-αβ pathway were dramatically increased by 24 h postinfection. However, the mRNA level of a single IFN-stimulated gene, MxA (myxovirus resistance A), the IFN-stimulated gene known to be critical in blocking influenza virus replication, was significantly lower in the tracheal lavages of untreated monkeys than in the oseltamivir-treated monkeys (p = 0.05). These results demonstrate for the first time that uncontrolled influenza A virus replication actively suppresses MxA gene expression and emphasize the critical role of innate immunity in controlling influenza virus replication in vivo.

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Section: Discussionmentioning

confidence: 99%

Interferon-Induced Expression of MxA in the Respiratory Tract of Rhesus Macaques Is Suppressed by Influenza Virus Replication

Carroll

Matzinger

Genescà

et al. 2008

The Journal of Immunology

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“…Type I IFNs are potent antiviral cytokines. They are activated by viral infection, including viral dsRNA or by-products of viral replication, and have a wide range of antiviral effects (Haller et al, 2006). Although potent antiviral factors from IFNs have been identified, many viruses have evolved various mechanisms to block or weaken the IFN system (de los Santos et al, 2006;Didcock et al, 1999;Fensterl et al, 2005;D.…”

Section: Introductionmentioning

confidence: 99%

Identification of the IFN-β response in H3N2 canine influenza virus infection

San

et al. 2016

Journal of General Virology

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Canine influenza viruses (CIVs) circulate continuously in the dog population, providing opportunities for exposure to humans and other species. Although the dog genome has been sequenced, innate immunity in dogs is not well characterized, which limits the understanding of H3N2 canine influenza virus pathogenesis. Equally, how this virus evades the canine host innate immune response to successfully establish infection remains unclear. To analyse the IFN-b response to CIV infection in Madin-Darby canine kidney cells, the canine IFN-b promoter sequence and its positive regulatory domain motifs were first cloned and identified using a luciferase reporter system. Next, we found that infection with the CIV strain GD/12 blocked the IFN-b response primarily by inhibiting the NF-k B and IFN regulatory factor 3 (IRF3) signalling pathways. Expression of GD/12 non-structural protein 1 alone was sufficient to inhibit Sendai virus-induced NF-k B and IRF3 activation by suppressing p65 and IRF3 phosphorylation, suggesting the important role of this protein in the CIV-mediated inhibition of the IFN-b response. These results suggest that inhibition of the IFN-b signalling pathway may have played a role in CIV establishment and spread in dog populations.

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“…Upon virus infection the type I interferon (IFN-a/b) response is one of the earliest innate host defence mechanisms, and many viruses have found means to avoid IFN gene expression Haller et al, 2006). Production of IFN-a/b is induced by the recognition of pathogen-associated molecular patterns (PAMP) (Medzhitov & Janeway, 2002) and initiates transcriptional upregulation of IFN-stimulated genes (ISGs) to establish an antiviral state.…”

Section: Introductionmentioning

confidence: 99%

Mouse cytomegalovirus inhibits beta interferon (IFN-β) gene expression and controls activation pathways of the IFN-β enhanceosome

Trilling

Zimmermann

et al. 2008

Journal of General Virology

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We have investigated beta interferon (IFN-b) and IFN-a4 gene expression and activation of related transcription factors in mouse cytomegalovirus (MCMV)-infected fibroblasts. mRNA analysis demonstrated an initial phase of IFN gene induction upon MCMV infection, which was followed by a sustained MCMV-mediated simultaneous downregulation of IFN-b and IFN-a4 gene expression. The induction of IFN transcription resulted from the activation of the components of the IFN-b enhanceosome, i.e. IFN regulatory factor (IRF) 3, nuclear factor (NF)-kB, activating transcription factor (ATF)-2 and c-Jun. Activation of the transcription factors occurred rapidly and in a sequential order upon infection, but only lasted a while. As a consequence, IFN-a/b gene expression became undetectable 6 h post-infection and throughout the MCMV replication cycle. This effect is based on an active interference since restimulation of IFN gene induction by further external stimuli (e.g. Sendai virus infection) was completely abolished. This inhibition required MCMV gene expression and was not observed in cells infected with UV-inactivated MCMV virions. The efficiency of inhibition is achieved by a concerted blockade of IkBa degradation and a lack of nuclear accumulation of IRF3 and ATF-2/c-Jun. Using an MCMV mutant lacking pM27, a signal transducer and activator of transcription (STAT) 2-specific inhibitor of Jak/STAT signalling, we found that the initial phase of IFN induction and the subsequent inhibition does not depend on the positive-IFN feedback loop. Our findings indicate that the MCMV-mediated downregulation of IFN transcription in fibroblasts relies on a large arsenal of inhibitory mechanisms targeting each pathway that contributes to the multiprotein enhanceosome complex. INTRODUCTIONUpon virus infection the type I interferon (IFN-a/b) response is one of the earliest innate host defence mechanisms, and many viruses have found means to avoid IFN gene expression Haller et al., 2006). Production of IFN-a/b is induced by the recognition of pathogen-associated molecular patterns (PAMP) (Medzhitov & Janeway, 2002) and initiates transcriptional upregulation of IFN-stimulated genes (ISGs) to establish an antiviral state. IFN-a/b synthesized by virus-infected cells bind to the IFN-a/b receptor complex, termed IFNAR, and activates the Jak/STAT signal transduction cascade, leading to the formation of the IFN-stimulated gene factor 3 (ISGF3). ISGF3 binds to IFN-stimulated response elements (ISRE), located in the promoter region of IFNinducible target genes mediating IFN effector functions (Darnell et al., 1994).Initiation of IFN transcription and its subsequent autocrine and paracrine amplification is a prerequisite for efficient IFN effector responses. IFN-b gene transcription is controlled by a higher order transcription enhancer complex, known as enhanceosome (Maniatis, 1986;Maniatis et al., 1998). The multi-component complex includes three distinct transcription factors binding cooperatively to the IFN-b promoter and the architectural high mobili...

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The interferon response circuit: Induction and suppression by pathogenic viruses

Cited by 601 publications

References 186 publications

Interferon-Induced Expression of MxA in the Respiratory Tract of Rhesus Macaques Is Suppressed by Influenza Virus Replication

Interferon-Induced Expression of MxA in the Respiratory Tract of Rhesus Macaques Is Suppressed by Influenza Virus Replication

Identification of the IFN-β response in H3N2 canine influenza virus infection

Mouse cytomegalovirus inhibits beta interferon (IFN-β) gene expression and controls activation pathways of the IFN-β enhanceosome

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