IgA targeting on the α-molecular recognition element (α-MoRE) of viral phosphoprotein inhibits measles virus replication by interrupting formation and function of P-N complex intracellularly
IgA targeting on the α-molecular recognition element (α-MoRE) of viral phosphoprotein inhibits measles virus replication by interrupting formation and function of P-N complex intracellularly
复制标题
靶向病毒磷蛋白α分子识别元件（α-MoRE）的 IgA 通过中断细胞内 P-N 复合物的形成和功能来抑制麻疹病毒复制
DOI：
10.1016/j.antiviral.2018.11.014
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发表时间：
2019-01-01
影响因子：
7.6
通讯作者：
Yan, Huimin
中科院分区：
文献类型：
--
作者：
Zhou, Dihan;Yang, Yi;Yan, Huimin
分泌型 IgA (SIgA) 抗体的独特之处在于其能够通过转胞吞作用穿过上皮细胞，因此有机会和可能性在病毒复制过程中与所有病毒成分相互作用，从而可能导致细胞内病毒复制的抑制。在这里，我们报道了一种针对麻疹病毒（MV）磷蛋白（P）的新型 IgA mAb 1D11-IgA，它能够与在两室 Transwell 系统中生长的 MV 感染的 Vero-pIgR 细胞中的 P 特异性相互作用。 1D11-IgA 的结合表位涉及 P 蛋白中的关键残基脯氨酸 23，它属于 P 的 α 分子识别元件 (α-MoRE)，对 N-0-P 复合物至关重要。该抗体似乎会阻止 P-N 复合物中的 P 与 N 相互作用，从而可能抑制病毒 RdRp 复合物的功能，从而导致病毒基因组 RNA 和 mRNA 的合成减少。我们的数据共同证明，IgA 能够与上皮细胞内的病毒磷蛋白相互作用，并通过中断 P-N 复合物的形成和 RdRp 的功能来中和病毒复制。研究结果强调，IgA 通过靶向对病毒复制至关重要的病毒保守成分而具有独特的抗病毒活性，这可作为单链病毒 P-N 界面成药性的概念验证评估。
Secretory IgA (SIgA) antibody is unique for its capability to transit through epithelial cells by transcytosis and thus has opportunities and probabilities to interact with all viral components during viral replication which may result in the inhibition of viral replication intracellularly. Here, we report a novel IgA mAb 1D11-IgA against phosphoprotein (P) of measles virus (MV), which is able to interact specifically with P in MV infected Vero-pIgR cells grown in a two-chamber transwell system. The binding epitope of 1D11-IgA involves a key residue proline 23 in P protein, which is among the alpha-molecular recognition element (alpha-MoRE) of P and critical for N-0-P complex. The antibody appears to block P to interact with N in P-N complex and thus may inhibit the function of viral RdRp complex, which results in decreased synthesis of viral genome RNA and mRNA. Our data together demonstrate that IgA is able to interact with viral phosphoprotein intraepithelial cells and neutralize viral replication by interrupting formation of P-N complex and function of RdRp. The findings highlight that IgA has a unique anti-viral activity by targeting viral conserved components critical for viral replication, which serves as a proof-of-concept assessment of the druggability of mononegavirales P-N interfaces.