HIV infection suppresses TLR3 activation-mediated antiviral immunity in microglia and macrophages.,Immunology

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HIV infection suppresses TLR3 activation-mediated antiviral immunity in microglia and macrophages.
Immunology ( IF 4.9 ) Pub Date : 2020-02-13 , DOI: 10.1111/imm.13181
Hang Liu _{1,

2} , Run-Hong Zhou ₂ , Yu Liu ₂ , Le Guo ₂ , Xu Wang ₂ , Wen-Hui Hu ₂ , Wen-Zhe Ho _{1,

2}

Affiliation

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.

中文翻译：

HIV 感染抑制小胶质细胞和巨噬细胞中 TLR3 激活介导的抗病毒免疫。

中枢神经系统（CNS）中的单核细胞谱系细胞，包括小胶质细胞和大脑巨噬细胞，是中枢神经系统针对病毒感染（包括人类免疫缺陷病毒（HIV））的先天免疫的关键角色。然而，这些细胞也是中枢神经系统中艾滋病毒的主要目标和储存库。为了解决 HIV 如何在中枢神经系统靶细胞中建立持续感染的问题，我们检查了 HIV 是否有能力抵消小胶质细胞和巨噬细胞中 Toll 样受体 3 (TLR3) 激活介导的抗病毒免疫。我们观察到，与未感染的对照细胞 (C20) 相比，HIV 潜伏感染的小胶质细胞 (HC69·5) 表达的 TLR3 和 TLR3 激活介导的干扰素 (IFN-α/β 和 IFN-λ) 水平降低。此外，人类原代巨噬细胞的HIV感染抑制了TLR3和IFN的表达。HIV 感染还抑制抗病毒 IFN 刺激基因 (ISG) 和 HIV 限制性 miRNA 的表达。从机制上讲，HIV感染抑制了HIV潜伏感染的小胶质细胞和急性感染的巨噬细胞中IFN调节因子（IRF3和IRF7）以及信号转导子和转录蛋白激活剂（STAT1和STAT3）的磷酸化。这些发现为艾滋病毒感染以及大脑中主要目标细胞和储存细胞的持续存在提供了以前未被认识的合理机制。

更新日期：2020-02-13

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