title: HIV-1 blocks the signaling adaptor MAVS to evade antiviral host defense after sensing of abortive HIV-1 RNA by the host helicase DDX3.
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.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Gringhuis
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Nina
authors.initials: N
authors.lastname: Hertoghs
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Kaptein
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Zijlstra-Willems
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Ramin
authors.initials: R
authors.lastname: Sarrami-Forooshani
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Joris K
authors.initials: JK
authors.lastname: Sprokholt
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Nienke H
authors.initials: NH
authors.lastname: van Teijlingen
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Booiman
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Karel A
authors.initials: KA
authors.lastname: van Dort
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Carla M S
authors.initials: CM
authors.lastname: Ribeiro
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Agata
authors.initials: A
authors.lastname: Drewniak
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002457:Cell Extracts; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics; D015331:Cohort Studies; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D057131:Immune Evasion; D007109:Immunity; D016899:Interferon-beta / Q000097:blood; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D015398:Signal Transduction; D019562:Viral Load / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002457:Cell Extracts; C505371:MAVS protein, human; D012367:RNA, Viral; D051192:Receptors, Pattern Recognition; D016899:Interferon-beta; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases