Type I interferon imposes a TSG101/ISG15 checkpoint at the Golgi for glycoprotein trafficking during influenza virus infection.

Type I interferon imposes a TSG101/ISG15 checkpoint at the Golgi for glycoprotein trafficking during influenza virus infection.
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DOI:
10.1016/j.chom.2013.10.011
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发表时间:
2013-11-13
影响因子:
30.3
通讯作者:
Ploegh HL
Ploegh HL
中科院分区:
医学1区
文献类型:
--
作者:
Sanyal S;Ashour J;Maruyama T;Altenburg AF;Cragnolini JJ;Bilate A;Avalos AM;Kundrat L;García-Sastre A;Ploegh HL

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几种包膜病毒利用宿主途径,如运输所需的细胞内体分选复合体(ESCRT)机制,进行组装和释放。甲型流感病毒(IAV)基质蛋白与ESCRT- i复合物结合,尽管诸如Tsg101等早期ESCRT蛋白参与IAV运输仍有待确定。我们发现Tsg101可以促进IAV运输,但这受到干扰素(IFN)刺激蛋白ISG15的有效限制。在感染的半完整细胞中,I型ifn处理细胞的胞浆可消除IAV血凝素(HA)向细胞表面的转运。这种抑制作用需要Tsg101,并且可以通过去isgylases来缓解。Tsg101本身在ifn处理的细胞中被isgayated。感染后,通过CRISPR/Cas9基因组编辑获得的完整的tsg101缺陷细胞在HA的表面展示和感染性病毒粒子释放方面存在缺陷。这些数据支持ifn在抑制流感病毒释放的分泌途径中诱导Tsg101/ isg15依赖性检查点的产生。
Several enveloped viruses exploit host pathways, such as the cellular endosomal sorting complex required for transport (ESCRT) machinery, for their assembly and release. The influenza A virus (IAV) matrix protein binds to the ESCRT-I complex, although the involvement of early ESCRT proteins such as Tsg101 in IAV trafficking remains to be established. We find that Tsg101 can facilitate IAV trafficking but this is effectively restricted by the interferon (IFN) stimulated protein ISG15. Cytosol from type I IFN-treated cells abolished IAV haemagglutinin (HA) transport to the cell surface in infected semi-intact cells. This inhibition required Tsg101 and could be relieved with deISGylases. Tsg101 is itself ISGylated in IFN-treated cells. Upon infection, intact Tsg101-deficient cells obtained by CRISPR/Cas9 genome editing were defective in surface display of HA and for infectious virion release. These data support the IFN-induced generation of a Tsg101/ISG15-dependent checkpoint in the secretory pathway that compromises influenza virus release.
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