The inducible amphisome isolates viral hemagglutinin and defends against influenza A virus infection.
The inducible amphisome isolates viral hemagglutinin and defends against influenza A virus infection.
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诱导型两性体分离病毒血凝素并防御甲型流感病毒感染。
DOI：
10.1038/s41467-019-13974-w
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Nishikawa K.
中科院分区：
文献类型：
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作者：
Omi J;Watanabe-Takahashi M;Igai K;Shimizu E;Tseng CY;Miyasaka T;Waku T;Hama S;Nakanishi R;Goto Y;Nishino Y;Miyazawa A;Natori Y;Yamashita M;Nishikawa K.
耐药甲型流感病毒 (IAV) 的出现需要开发新型抗 IAV 药物。在这里，我们使用多价肽库筛选来靶向 IAV 血凝素 (HA) 蛋白，并鉴定出 PVF-tet（一种基于肽的 HA 抑制剂）。 PVF-tet 通过与新合成的 HA（而不是亲本病毒的 HA）结合来抑制 IAV 的细胞病变和增殖，从而诱导 HA 在独特的结构（诱导型两栖体）中积累，PVF-tet 加速了自噬体的产生。在没有 PVF-tet 的情况下，过表达 ABC 转运蛋白亚家族 A3 的细胞也会产生两性体，以响应 IAV 感染，该亚家族 A3 在多囊泡核内体成熟为层状体（一种脂质分选细胞器）中发挥着重要作用。我们的结果表明，诱导型两性体可以通过隔离 HA 作为一种基于细胞器的抗病毒机制。 PVF-tet 有效地拯救了 IAV 感染致死的小鼠。
The emergence of drug-resistant influenza type A viruses (IAVs) necessitates the development of novel anti-IAV agents. Here, we target the IAV hemagglutinin (HA) protein using multivalent peptide library screens and identify PVF-tet, a peptide-based HA inhibitor. PVF-tet inhibits IAV cytopathicity and propagation in cells by binding to newly synthesized HA, rather than to the HA of the parental virus, thus inducing the accumulation of HA within a unique structure, the inducible amphisome, whose production from the autophagosome is accelerated by PVF-tet. The amphisome is also produced in response to IAV infection in the absence of PVF-tet by cells overexpressing ABC transporter subfamily A3, which plays an essential role in the maturation of multivesicular endosomes into the lamellar body, a lipid-sorting organelle. Our results show that the inducible amphisomes can function as a type of organelle-based anti-viral machinery by sequestering HA. PVF-tet efficiently rescues mice from the lethality of IAV infection.