HIV-1 Blocks the Signaling Adaptor MAVS to Evade Antiviral Host Defense After Sensing of Abortive HIV-1 RNA by the Host Helicase DDX3

Overview

Journal Nat Immunol

Date 2016 Dec 27

PMID 28024153

Citations 68

Authors

Sonja I Gringhuis

Nina Hertoghs

Tanja M Kaptein

Esther M Zijlstra-Willems

Ramin Sarrami-Forooshani

Joris K Sprokholt

Nienke H van Teijlingen

Neeltje A Kootstra

Thijs Booiman

Karel A van Dort

Carla M S Ribeiro

Agata Drewniak

Teunis B H Geijtenbeek

Affiliations

Soon will be listed here.

Abstract

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.

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