Influenza Virus Neuraminidase Engages CD83 and Promotes Pulmonary Injury
Influenza Virus Neuraminidase Engages CD83 and Promotes Pulmonary Injury
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DOI：
10.1128/jvi.01753-20
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发表时间：
2021-02-01
影响因子：
5.4
通讯作者：
Zhang，Zongde
中科院分区：
文献类型：
--
作者：
Ma，Ning;Li，Xingjie;Zhang，Zongde
甲型流感病毒会导致人类和动物的严重呼吸道疾病。对流感病毒感染的先天免疫反应过度会导致高细胞分裂素血症，这是导致死亡和发病率的原因。然而，流感引起高细胞分裂素血症的机制还不完全清楚。在这项研究中，我们建立了一种小鼠适应的H9N2病毒MA01，以评估肺部对流感的先天免疫反应。MA01感染可引起高水平的细胞因子释放，加重小鼠肺损伤，并上调肺内树突状细胞和巨噬细胞CD83蛋白表达。流感病毒神经氨酸酶(NA)揭示了CD83蛋白，并导致了高水平的细胞因子。此外，我们还提供了CD83是唾液酸化糖蛋白的证据。神经氨酸酶处理可增强脂多糖刺激的RAW264.7细胞中的NF-κB活性。抗CD83治疗可减轻流感病毒所致的小鼠肺损伤。我们的研究表明，流感病毒神经氨酸酶调节CD83状态，并参与“细胞因子风暴”，这可能为抑制这种免疫损伤提供新的方法。重要的是，循环中炎症介质的大量释放是甲型流感病毒感染过程中肺损伤的原因。这种现象被称为“细胞因子风暴”。然而，流感引发细胞因子风暴的机制尚不完全清楚。在这项研究中，我们发现神经氨酸酶揭开了肺中CD83蛋白的面纱，并导致了高水平的细胞因子。抗CD83治疗可减轻肺组织免疫损伤。NA-CD83轴可能是阻断流感引起的肺损伤的靶点。
Influenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza virus infection results in hypercytokinemia, which is responsible for mortality and morbidity. However, the mechanism by which influenza induces hypercytokinemia is not fully understood. In this study, we established a mouse-adapted H9N2 virus, MA01, to evaluate the innate immune response to influenza in the lung. MA01 infection caused high levels of cytokine release, enhanced pulmonary injury in mice, and upregulated CD83 protein in dendritic cells and macrophages in the lung. Influenza virus neuraminidase (NA) unmasked CD83 protein and contributed to high cytokine levels. Furthermore, we provide evidence that CD83 is a sialylated glycoprotein. Neuraminidase treatment enhanced lipopolysaccharide (LPS)-stimulated NF-κB activation in RAW264.7 cells. Anti-CD83 treatment alleviated influenza virus-induced lung injury in mice. Our study indicates that influenza virus neuraminidase modulates CD83 status and contributes to the “cytokine storm,” which may suggest a new approach to curb this immune injury.IMPORTANCEThe massive release of circulating mediators of inflammation is responsible for lung injury during influenza A virus infection. This phenomenon is referred to as the “cytokine storm.” However, the mechanism by which influenza induces the cytokine storm is not fully understood. In this study, we have shown that neuraminidase unmasked CD83 protein in the lung and contributed to high cytokine levels. Anti-CD83 treatment could diminish immune damage to lung tissue. The NA-CD83 axis may represent a target for an interruption of influenza-induced lung damage.