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[Online ahead of print]

Respirovirus C Protein Inhibits Activation of Type I Interferon Receptor-Associated Kinases to Block JAK-STAT Signaling

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Respirovirus C Protein Inhibits Activation of Type I Interferon Receptor-Associated Kinases to Block JAK-STAT Signaling

Yoshinori Kitagawa et al. FEBS Lett.

Abstract

Respirovirus C protein blocks the type I interferon (IFN)-stimulated activation of the JAK-STAT pathway. It has been reported that C protein inhibits IFN-α-stimulated tyrosine phosphorylation of STATs, but the underlying mechanism is poorly understood. Here, we show that the C protein of Sendai virus (SeV), a member of the Respirovirus genus, binds to the IFN receptor subunit IFN-α/β receptor subunit (IFNAR)2 and inhibits IFN-α-stimulated tyrosine phosphorylation of the upstream receptor-associated kinases, JAK1 and TYK2. Analysis of various SeV C mutant (Cm) proteins demonstrates the importance of the inhibitory effect on receptor-associated kinase phosphorylation for blockade of JAK-STAT signaling. Furthermore, this inhibitory effect and the IFNAR2 binding capacity are observed for all the respirovirus C proteins examined. Our results suggest that respirovirus C protein inhibits activation of the receptor-associated kinases JAK1 and TYK2 possibly through interaction with IFNAR2.

Keywords: C protein; JAK-STAT pathway; JAK1; Sendai virus; TYK2; interferon; respirovirus.

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References

    1. Adams MJ, Lefkowitz EJ, King AMQ, Harrach B, Harrison RL, Knowles NJ, Kropinski AM, Krupovic M, Kuhn JH, Mushegian AR et al. (2017) Changes to taxonomy and the international code of virus classification and nomenclature ratified by the International Committee on Taxonomy of Viruses (2017). Arch Virol 162, 2505-2538.
    1. Platanias LC (2005) Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 5, 375-386.
    1. Villarino AV, Kanno Y and O'Shea JJ (2017) Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol 18, 374-384.
    1. Stark GR, Cheon H and Wang Y (2018) Responses to cytokines and interferons that depend upon JAKs and STATs. Cold Spring Harb Perspect Biol 10, a028555.
    1. Garcin D, Latorre P and Kolakofsky D (1999) Sendai virus C proteins counteract the interferon-mediated induction of an antiviral state. J Virol 73, 6559-6565.

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