Chapter 6 : Jak-Stat Pathway in Response to Virus Infection

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The source, amount, and kinetics of type I interferon (IFN) production are dependent on the nature of the viral pathogen and will be determined by the susceptible cell type, the target organ(s), and the range of host sensors exposed to viral products. While it is not certain that double-stranded RNA (dsRNA) intermediates are produced during the course of negative-strand RNA virus infection, it has recently been demonstrated that single-stranded RNAs with free 5’-triphosphates generated in the course of measles virus infection will bind and activate retinoic acid-inducible gene I (RIG-I). IL-6 and tumor necrosis factor-α have also been reported in influenza virus infection. It would be premature to conclude from this preliminary characterization that IFN-λ's do not play an important role in host defense against virus infection despite the fact that animals deficient in IFN-λ signaling did not show the extreme sensitivity of IFN-αR receptor (IFNAR)1 mice to systemic vesicular stomatitis virus (VSV) and encephalomyocarditis virus challenge. Many viruses promote the inhibition or degradation of IRF3, and there are many examples of viruses directly targeting the Jak-Stat pathway. Taken together, these results suggest that many viruses encountered in nature have evolved very effective anti-IFN and anti-Stat strategies and that redundant pathways are also important for resisting virus infection.

Citation: Durbin J. 2009. Jak-Stat Pathway in Response to Virus Infection, p 75-90. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch6

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Figure 1

Stat activation and ISG induction by IFN-α/β and IFN-γ.

Citation: Durbin J. 2009. Jak-Stat Pathway in Response to Virus Infection, p 75-90. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch6
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Figure 2

Conserved elements of Stat proteins. This consists of the conserved amino-terminal domain, the coiled-coil domain, the DNA-binding domain, a linker domain, the SH2 domain, and the transcriptional activation domain (TAD). The tyrosine residue necessary for Stat activation is present at approximately residue 700 in each of the Stat proteins.

Citation: Durbin J. 2009. Jak-Stat Pathway in Response to Virus Infection, p 75-90. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch6
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Figure 3

Type I IFN induction by virus infection mediated by RIG-I/MDA-5. MAVS acts as an adaptor protein which binds to both RIG-1/MDA-5 and TRAF3 (tumor necrosis factor receptor-associated factor 3). TRAF3 binds TBK1 and IKK-ε directly in a complex which also involves TANK (TRAF family member-associated NF-κB activator).

Citation: Durbin J. 2009. Jak-Stat Pathway in Response to Virus Infection, p 75-90. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch6
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Table 1

Stat activation by cytokines and growth factors

Citation: Durbin J. 2009. Jak-Stat Pathway in Response to Virus Infection, p 75-90. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch6
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Table 2

Susceptibility of Stat knockout mice to viral pathogens

Citation: Durbin J. 2009. Jak-Stat Pathway in Response to Virus Infection, p 75-90. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch6

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