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Review

Mechanisms underlying the inhibition of interferon signaling by viruses

Pages 270-277 | Received 27 Sep 2013, Accepted 17 Jan 2014, Published online: 06 Feb 2014

Figures & data

Figure 1. A summary of signaling pathways leading to the induction of interferons. Viral entry is followed by the release of the viral genome into host cells, triggering the activation of TLRs, or cytoplasmic viral sensors (RIG1 and MDA5), or the activation of the NFκB, AP-1, IRF-3, and IRF-7 signaling pathways. Collectively, these pathways lead to the induction of interferons α and β, which are encoded by the IFNA and IFNB genes respectively.

Figure 1. A summary of signaling pathways leading to the induction of interferons. Viral entry is followed by the release of the viral genome into host cells, triggering the activation of TLRs, or cytoplasmic viral sensors (RIG1 and MDA5), or the activation of the NFκB, AP-1, IRF-3, and IRF-7 signaling pathways. Collectively, these pathways lead to the induction of interferons α and β, which are encoded by the IFNA and IFNB genes respectively.

Figure 2. A summary of viral mechanisms that inhibit the upstream mediators of interferon induction. NS1 and Z proteins target RIG-1, V proteins target MDA-5, and RSV targets TLRs 7 and 8.

Figure 2. A summary of viral mechanisms that inhibit the upstream mediators of interferon induction. NS1 and Z proteins target RIG-1, V proteins target MDA-5, and RSV targets TLRs 7 and 8.

Figure 3. A summary of viral mechanisms that target the IRF-3, NFκB, and AP-1 signaling pathways. E6, NS1, and Npro target IRF-3; NS1, 3C, and L(pro) target NFκB; NS1 and NS5A target AP-1.

Figure 3. A summary of viral mechanisms that target the IRF-3, NFκB, and AP-1 signaling pathways. E6, NS1, and Npro target IRF-3; NS1, 3C, and L(pro) target NFκB; NS1 and NS5A target AP-1.

Figure 4. A summary of viral mechanisms that target the JAK-STAT signaling pathway. NS5 and V proteins prevent the activation of TYK2 and JAK1 respectively; V proteins are also involved in STAT sequestration. NS5 and SV5 degrade STAT proteins; C proteins prevent the formation of activated STAT dimers and HCV core proteins induce SOCS expression. ISRE, interferon stimulated response element; GAS, gamma interferon activation site.

Figure 4. A summary of viral mechanisms that target the JAK-STAT signaling pathway. NS5 and V proteins prevent the activation of TYK2 and JAK1 respectively; V proteins are also involved in STAT sequestration. NS5 and SV5 degrade STAT proteins; C proteins prevent the formation of activated STAT dimers and HCV core proteins induce SOCS expression. ISRE, interferon stimulated response element; GAS, gamma interferon activation site.