Arginine-rich histones have strong antiviral activity for influenza A viruses.
Arginine-rich histones have strong antiviral activity for influenza A viruses.
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DOI：
10.1177/1753425915593794
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发表时间：
2015-10
期刊：
影响因子：
3.2
通讯作者：
Hartshorn KL
中科院分区：
文献类型：
--
作者：
Hoeksema M;Tripathi S;White M;Qi L;Taubenberger J;van Eijk M;Haagsman H;Hartshorn KL
虽然组蛋白以DNA结合和转录调节特性而闻名，但它们也对广泛的潜在致病生物体具有抗菌活性。组蛋白在中性粒细胞胞外陷阱中丰富，在NET介导的抗菌剂杀伤中发挥重要作用。在这里，我们显示了组蛋白对季节性H3 N2和H1N1的抗流感活性，但对大流行性H1N1没有。富含精氨酸的组蛋白H3和H4比富含赖氨酸的组蛋白H2 A和H2 B具有更大的中和和病毒聚集活性。在所有核心组蛋白中，组蛋白H4在中和IAV方面最有效，并且当通过qRT-PCR测量时，用IAV与组蛋白H4孵育导致上皮细胞的摄取和病毒复制减少。组蛋白H4的抗病毒活性主要通过对病毒颗粒的直接作用介导。组蛋白H4与IAV结合，如通过ELISA和H4与IAV的共沉降所评估的。H4还诱导聚集，如通过共聚焦显微镜和光透射测定所评估的。尽管对季节性IAV株有很强的抗病毒活性，但H4对大流行性H1N1没有活性。这些发现表明组蛋白在针对IAV的先天免疫应答中可能起作用。
While histones are best known for DNA binding and transcription-regulating properties, they also have antimicrobial activity against a broad range of potentially pathogenic organisms. Histones are abundant in neutrophil extracellular traps, where they play an important role in NET-mediated antimicrobial killing. Here, we show anti-influenza activity of histones against both seasonal H3N2 and H1N1, but not pandemic H1N1. The arginine rich histones, H3 and H4, had greater neutralizing and viral aggregating activity than the lysine rich histones, H2A and H2B. Of all core histones, histone H4 is most potent in neutralizing IAV, and incubation with IAV with histone H4 results in a decrease in uptake and viral replication by epithelial cells when measured by qRT-PCR. The antiviral activity of histone H4 is mediated principally by direct effects on viral particles. Histone H4 binds to IAV as assessed by ELISA and co-sedimentation of H4 with IAV. H4 also induces aggregation, as assessed by confocal microscopy and light transmission assays. Despite strong antiviral activity against the seasonal IAV strains, H4 was inactive against pandemic H1N1. These findings indicate a possible role for histones in the innate immune response against IAV.