LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation

• DOI: 10.3389/fmicb.2022.849020
• Publication Date: 2022-04-13T13:51:46Z
• Authors: Yongheng Yang; Mengyun Li; Yongtao Ma; Wei Ye; Yue Si; Xuyang Zheng; He Liu; Linfeng Cheng; Liang Zhang; Hui Zhang; Xijing Zhang; Yingfeng Lei; Lixin Shen; Fanglin Zhang; Hongwei Ma
• Keywords: Hantaan virus

As the global prototypical zoonotic hantavirus, Hantaan virus (HTNV) is prevalent in Asia and leading causative agent of severe hemorrhagic fever with renal syndrome (HFRS), which has profound morbidity mortality. Macrophages are crucial components host innate immune system serve as first line defense against HTNV infection. Previous studies indicated that viral replication efficiency macrophages determines hantavirus pathogenicity, but it remains unknown factor manipulates macrophage activation pattern virus-host interaction process. Here, we performed transcriptomic analysis HTNV-infected mouse bone marrow-derived identified long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1), especially isoform NEAT1-2, one lncRNAs differentially expressed at early phase. Based on coculture experiments, revealed silencing NEAT1-2 hinders inflammatory facilitates propagation, while enhancing transcription effectively restrains replication. Furthermore, sterol response element binding factor-2 (SREBP2), controls cholesterol metabolism process, was found to stimulate by promoting production multiple cytokines upon could potentiate SREBP2 activity upregulating Srebf1 expression interacting SREBP2, thus stimulating limiting propagation. More importantly, demonstrated level patient monocytes negatively correlated load HFRS disease progression. Our results a function mechanism action for lncRNA NEAT1 heightening SREBP2-mediated restrain hantaviral propagation association severity.