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Lyssavirus matrix protein cooperates with phosphoprotein to modulate the Jak-Stat pathway

Abstract : Phosphoprotein (P) and matrix protein (M) cooperate to undermine the immune response to rabies virus (RABV) infections. While P is involved in the modulation of the Jak-Stat pathway through the cytoplasmic retention of interferon (IFN)-activated STAT1 (pSTAT1), M interacts with the RelAp43-p105-ABIN2-TPL2 complex, to efficiently inhibit the nuclear factor-κB (NF-κB) pathway. Using transfections, protein-complementation assays, reverse genetics and DNA ChIP, we identified a role of M protein in the control of Jak-Stat signaling pathway, in synergy with the P protein. In unstimulated cells, both M and P proteins were found to interact with JAK1. Upon type-I IFN stimulation, the M switches toward pSTAT1 interaction, which results in an enhanced capacity of P protein to interact with pSTAT1 and restrain it in the cytoplasm. Furthermore, the role for M-protein positions 77, 100, 104 and 110 was also demonstrated in interaction with both JAK1 and pY-STAT1, and confirmed in vivo. Together, these data indicate that M protein cooperates with P protein to restrain in parallel, and sequentially, NF-κB and Jak-Stat pathways.
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Submitted on : Monday, June 15, 2020 - 4:23:00 PM
Last modification on : Friday, June 19, 2020 - 3:30:56 AM

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Florian Sonthonnax, Benoit Besson, Emilie Bonnaud, Grégory Jouvion, David Merino, et al.. Lyssavirus matrix protein cooperates with phosphoprotein to modulate the Jak-Stat pathway. Scientific Reports, Nature Publishing Group, 2019, 9 (1), pp.12171. ⟨10.1038/s41598-019-48507-4⟩. ⟨pasteur-02868844⟩

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