HIV infection suppresses TLR3 activation‐mediated antiviral immunity in microglia and macrophages

Summary Monocytic‐lineage cells in the central nervous system (CNS), including microglia and brain resident macrophages, are the key players in the CNS innate immunity against viral infections, including human immunodeficiency virus (HIV). However, these cells also serve as the major targets and res...

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Bibliographic Details
Published in:Immunology 2020-07, Vol.160 (3), p.269-279
Main Authors: Liu, Hang, Zhou, Run‐Hong, Liu, Yu, Guo, Le, Wang, Xu, Hu, Wen‐Hui, Ho, Wen‐Zhe
Format: Article
Language:English
Subjects:
Activation
Brain
Central nervous system
HIV
Human immunodeficiency virus
Immunity
Infections
Innate immunity
Interferon
Interferon regulatory factor 3
Interferon regulatory factor 7
Latent infection
macrophage
Macrophages
Microglia
Microglial cells
Monocytes
Original
Phosphorylation
Stat1 protein
Stat3 protein
TLR3 protein
Toll-like receptors
Toll‐like receptor 3
Transcription
Viruses
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Summary:Summary Monocytic‐lineage cells in the central nervous system (CNS), including microglia and brain resident macrophages, are the key players in the CNS innate immunity against viral infections, including human immunodeficiency virus (HIV). However, these cells also serve as the major targets and reservoirs for HIV in the CNS. To address the question of how HIV can establish persistent infection in the target cells in the CNS, we examined whether HIV has the ability to counteract Toll‐like receptor 3 (TLR3) activation‐mediated antiviral immunity in microglia and macrophages. We observed that HIV latently infected microglial cells (HC69·5) expressed reduced levels of TLR3 and TLR3 activation‐mediated interferons (IFN‐α/β and IFN‐λ) as compared with the uninfected control cells (C20). In addition, HIV infection of primary human macrophages suppressed the expression of TLR3 and the IFNs. HIV infection also inhibited the expression of the antiviral IFN‐stimulated genes (ISGs) and the HIV‐restriction miRNAs. Mechanistically, HIV infection inhibited the phosphorylation of IFN regulatory factors (IRF3 and IRF7) and signal transducer and activator of transcription proteins (STAT1 and STAT3) in both HIV latently infected microglia and acutely infected macrophages. These findings provide previously unrecognized and sound mechanisms for HIV infection and persistence in the primary target and reservoir cells in the brain. HIV infection suppresses TLR3‐IFN signalling activation and inhibits the expression of multiple intracellular antiviral factors (IFNs, ISGs and HIV‐restriction miRNAs) in microglial cells and macrophages.
ISSN:0019-2805
1365-2567
DOI:10.1111/imm.13181