TY - JOUR
T1 - HIV-1 blocks the signaling adaptor MAVS to evade antiviral host defense after sensing of abortive HIV-1 RNA by the host helicase DDX3
AU - Gringhuis, Sonja I.
AU - Hertoghs, Nina
AU - Kaptein, Tanja M.
AU - Zijlstra-Willems, Esther M.
AU - Sarrami-Fooroshani, Ramin
AU - Sprokholt, Joris K.
AU - van Teijlingen, Nienke H.
AU - Kootstra, Neeltje A.
AU - Booiman, Thijs
AU - van Dort, Karel A.
AU - Ribeiro, Carla M. S.
AU - Drewniak, Agata
AU - Geijtenbeek, Teunis B. H.
PY - 2017
Y1 - 2017
N2 - The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS. Notably, HIV-1 recognition by the C-type lectin receptor DC-SIGN activated the mitotic kinase PLK1, which suppressed signaling downstream of MAVS, thereby interfering with intrinsic host defense during HIV-1 infection. Finally, we showed that PLK1-mediated suppression of DDX3-MAVS signaling was a viral strategy that accelerated HIV-1 replication in infected individuals
AB - The mechanisms by which human immunodeficiency virus 1 (HIV-1) avoids immune surveillance by dendritic cells (DCs), and thereby prevents protective adaptive immune responses, remain poorly understood. Here we showed that HIV-1 actively arrested antiviral immune responses by DCs, which contributed to efficient HIV-1 replication in infected individuals. We identified the RNA helicase DDX3 as an HIV-1 sensor that bound abortive HIV-1 RNA after HIV-1 infection and induced DC maturation and type I interferon responses via the signaling adaptor MAVS. Notably, HIV-1 recognition by the C-type lectin receptor DC-SIGN activated the mitotic kinase PLK1, which suppressed signaling downstream of MAVS, thereby interfering with intrinsic host defense during HIV-1 infection. Finally, we showed that PLK1-mediated suppression of DDX3-MAVS signaling was a viral strategy that accelerated HIV-1 replication in infected individuals
U2 - https://doi.org/10.1038/ni.3647
DO - https://doi.org/10.1038/ni.3647
M3 - Article
C2 - 28024153
SN - 1529-2908
VL - 18
SP - 225
EP - 235
JO - Nature immunology
JF - Nature immunology
IS - 2
ER -