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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-?B (NF-?B) 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-?B and Jak-Stat pathways.

SUBMITTER: Sonthonnax F 

PROVIDER: S-EPMC6704159 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Sonthonnax Florian F   Besson Benoit B   Bonnaud Emilie E   Jouvion Grégory G   Merino David D   Larrous Florence F   Bourhy Hervé H  

Scientific reports 20190821 1


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 t  ...[more]

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