Immunoglobulin A Targeting on the N-Terminal Moiety of Viral Phosphoprotein Prevents Measles Virus from Evading Interferon-fl Signaling
Immunoglobulin A Targeting on the N-Terminal Moiety of Viral Phosphoprotein Prevents Measles Virus from Evading Interferon-fl Signaling
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免疫球蛋白 A 靶向病毒磷蛋白 N 端部分可防止麻疹病毒逃避干扰素-fl 信号转导
DOI：
10.1021/acsinfecdis.9b00427
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发表时间：
2020-05-08
影响因子：
5.3
通讯作者：
Yan, Huimin
中科院分区：
文献类型：
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作者：
Yang, Yi;Zhou, Dihan;Yan, Huimin
免疫球蛋白 A (IgA) 在跨上皮细胞转运过程中可以抑制细胞内病毒复制。我们发现了一种针对麻疹病毒 (MV) 磷蛋白 (PNT) N 端部分的单克隆 IgA 抗体 7F1-IgA，它在 Caco-2 细胞中抑制 MV 的细胞内复制，但在干扰素缺陷的 Vero-pIgR 细胞中则不抑制 MV 的细胞内复制。 7F1-IgA 穿过 MV 感染的 Caco-2 细胞的转胞吞作用增强了干扰素-β (IFN-β) 的产生和 IFN 刺激基因的表达，使 Caco-2 细胞具有更高的抗病毒免疫力。 7F1-IgA 与 MV 感染的 Caco-2 细胞内的 MV 磷蛋白特异性相互作用，并防止 MV 磷蛋白抑制 JAK1 和 STAT1 的磷酸化。 7F1-IgA 和病毒磷蛋白之间的上皮内相互作用导致 JAK1 和 STAT1 更早、更强的磷酸化，从而使 STAT1 更有效地核转位，从而激活 I 型干扰素途径。因此，针对磷蛋白的 IgA 可防止病毒逃避 I 型 IFN 信号传导，并赋予宿主上皮细胞有效的先天抗病毒免疫，从而增强新的抗病毒靶点和抗病毒策略。
Immunoglobulin A (IgA) can inhibit intracellular viral replication during its transport across the epithelial cells. We find a monoclonal IgA antibody 7F1-IgA against the N-terminal moiety of the phosphoprotein (PNT) of measles virus (MV), which inhibits the intracellular replication of MV in Caco-2 cells but not in interferon-deficient Vero-pIgR cells. Transcytosis of 7F1-IgA across the MV-infected Caco-2 cells enhances the production of interferon-beta (IFN-beta) and the expression of IFN-stimulated genes, rendering Caco-2 cells with higher antiviral immunity. 7F1-IgA specifically interacts with MV phosphoprotein inside the MV-infected Caco-2 cell and prevents MV phosphoprotein from inhibiting the phosphorylation of JAK1 and STAT1. The intraepithelial interaction between 7F1-IgA and the viral phosphoprotein results in an earlier and stronger phosphorylation of JAK1 and STAT1 and, consequently, a more efficient nuclear translocation of STAT1 for the activation of the type I interferon pathway. Thus, IgA against phosphoprotein prevents a virus from evading type I IFN signaling and confers host epithelial cells efficient innate antiviral immunity, which potentiates a new antiviral target and an antiviral strategy.