The VP3 Protein of Bluetongue Virus Associates with the MAVS Complex and Interferes with the RIG-I-Signaling Pathway

Abstract

Bluetongue virus (BTV), an arbovirus transmitted by Culicoides biting midges, is a major concern of wild and domestic ruminants. While BTV induces type I interferon (alpha/beta interferon [IFN-α/β]) production in infected cells, several reports have described evasion strategies elaborated by this virus to dampen this intrinsic, innate response. In the present study, we suggest that BTV VP3 is a new viral antagonist of the IFN-β synthesis. Indeed, using split luciferase and coprecipitation assays, we report an interaction between VP3 and both the mitochondrial adapter protein MAVS and the IRF3-kinase IKKε. Overall, this study describes a putative role for the BTV structural protein VP3 in the control of the antiviral response.

The Interplay between Bluetongue Virus Infections and Adaptive Immunity

“…NS1 promotes viral protein expression [ 25 ]; NS2 is an RNA binding protein which is the main component of viral inclusion bodies [ 26 ]; while NS3 is involved in virion egress [ 27 , 28 , 29 ]. VP3, NS3, NS4, and the putative NS5 are involved in impairing the host cellular response to BTV by acting as interferon antagonist and/or by promoting cellular shut-off [ 30 , 31 , 32 , 33 , 34 , 35 ].…”

Inhibition of the IFN Response by Bluetongue Virus: The Story So Far

“…Recently, the interference with IFN induction mediated by the inner core protein VP3 was further characterized ( Pourcelot et al, 2021 ). VP3 is important in virus assembly and has been shown to interact with NS2 in virus inclusion bodies ( Kar et al, 2005 ; Mohl and Roy, 2014 ).…”

“…VP3 is important in virus assembly and has been shown to interact with NS2 in virus inclusion bodies ( Kar et al, 2005 ; Mohl and Roy, 2014 ). VP3 could impair the IFN-β promoter activity in a dose dependent manner in reporter assays, and limit ISG56 induction ( Pourcelot et al, 2021 ). VP3 was shown to interact with MAVS and IKKε downstream of RIG-I activation ( Pourcelot et al, 2021 ).…”

“…VP3 could impair the IFN-β promoter activity in a dose dependent manner in reporter assays, and limit ISG56 induction ( Pourcelot et al, 2021 ). VP3 was shown to interact with MAVS and IKKε downstream of RIG-I activation ( Pourcelot et al, 2021 ). More precisely, Pourcelot et al (2021) mapped the interaction of VP3 to the C-terminal region of MAVS.…”

“…VP3 was shown to interact with MAVS and IKKε downstream of RIG-I activation ( Pourcelot et al, 2021 ). More precisely, Pourcelot et al (2021) mapped the interaction of VP3 to the C-terminal region of MAVS. This region contains a TRAF-interacting motif required for the correct activation of the IFN response as well as a regulatory binding site that recruits IKKε after MAVS ubiquitination on lysine 500 ( Paz et al, 2011 ).…”