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.
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Cell Extracts
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Clustered Regularly Interspaced Short Palindromic Repeats / genetics
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Cohort Studies
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DEAD-box RNA Helicases / metabolism
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Dendritic Cells / immunology
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Dendritic Cells / virology*
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Gene Expression Regulation, Viral
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HEK293 Cells
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HIV Infections / immunology*
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HIV Infections / virology
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HIV-1 / physiology*
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Host-Pathogen Interactions / genetics
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Humans
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Immune Evasion*
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Immunity*
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Interferon-beta / blood
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Macrophages / immunology
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Macrophages / virology*
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Polymorphism, Single Nucleotide
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RNA, Viral / immunology
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RNA, Viral / metabolism
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Receptors, Pattern Recognition / metabolism
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Signal Transduction
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Viral Load / genetics
Substances
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Adaptor Proteins, Signal Transducing
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Cell Extracts
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MAVS protein, human
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RNA, Viral
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Receptors, Pattern Recognition
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Interferon-beta
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DDX3X protein, human
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DEAD-box RNA Helicases