J Virol. 2009 Feb;83(3):1299-311. Epub 2008 Nov 26.

MAVS dimer is a crucial signaling component of innate immunity and the target of hepatitis C virus NS3/4A protease.External

Baril, M., Racine, M. E., Penin, F., Lamarre, D.,
--- - Institut de Recherche en Immunologie et en Cancerologie (IRIC), Montreal, Quebec, Canada.
The mitochondrial antiviral signaling (MAVS) protein plays a central role in innate antiviral immunity. Upon recognition of a virus, intracellular receptors of the RIG-I-like helicase family interact with MAVS to trigger a signaling cascade. In this study, we investigate the requirement of the MAVS structure for enabling its signaling by structure-function analyses and resonance energy transfer approaches in live cells. We now report the essential role of the MAVS oligomer in signal transduction and map the transmembrane domain as the main determinant of dimerization. A combination of mutagenesis and computational methods identified a cluster of residues making favorable van der Waals interactions at the MAVS dimer interface. We also correlated the activation of IRF3 and NF-kappaB with MAVS oligomerization rather than its mitochondrial localization. Finally, we demonstrated that MAVS oligomerization is disrupted upon expression of HCV NS3/4A protease, suggesting a mechanism for the loss of antiviral signaling. Altogether, our data suggest that the MAVS oligomer is essential in the formation of a multiprotein membrane-associated signaling complex and enables downstream activation of IRF3 and NF-kappaB in antiviral innate immunity.
PMID: 19036819External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD MAVS Link MAVS Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 19036819
CARD MAVS Link MAVS Fluorescence resonance energy transfer Huh 7 Not specified Not specified Not specified Not specified 19036819
CARD MAVS Link RIG-1 Fluorescence resonance energy transfer Huh 7 Not specified Not specified Not specified Not specified 19036819
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
CARD MAVS Link MAVS Luciferase assay NF-kB activation 19036819
CARD MAVS Link MAVS Luciferase assay NF-kB activation 19036819
(Link: click this icon to show interactions only between the two corresponding DDs)