The encephalomyocarditis virus Leader promotes the release of virions inside extracellular vesicles via the induction of secretory autophagy.
The encephalomyocarditis virus Leader promotes the release of virions inside extracellular vesicles via the induction of secretory autophagy.
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DOI：
10.1038/s41467-022-31181-y
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发表时间：
2022-06-24
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
裸病毒可以在通过细胞外囊泡（EV）释放诱导裂解之前逃离宿主细胞。这些纳米级的 EV 将分泌的病毒颗粒隐藏在宿主来源的膜中，从而改变病毒与宿主的相互作用，从而影响感染效率和抗病毒免疫力。目前，人们对调节这种病毒释放形式的病毒和宿主因素知之甚少。在这里，我们评估了脑心肌炎病毒（EMCV）领导蛋白的作用，这是一种破坏宿主抗病毒反应的“病毒安全蛋白”。使用高分辨率流式细胞术在单颗粒水平上表征野生型病毒或前导缺陷突变体感染后的 EV 释放。 Leader 的灭活消除了感染过程中 EV 的诱导，并大大减少了 EV 包裹的病毒释放。我们证明 Leader 通过刺激自噬的分泌臂来促进 EV 内病毒颗粒的释放。 EMCV Leader 的这一新发现的作用增加了该蛋白影响病毒-宿主相互作用的多种机制。此外，这些数据提供了第一个证据，证明非结构病毒蛋白通过包装在 EV 中，在小核糖核酸病毒的非裂解性释放中发挥着至关重要的作用。小核糖核酸病毒可以通过包装在细胞外囊泡 (EV) 中逃离受感染的细胞。在这里，范德格赖因等人。研究表明，脑心肌炎病毒（EMCV）的非结构前导蛋白促进 EV 包裹的病毒颗粒的释放，并为分泌性自噬在此过程中的作用提供了证据。
Naked viruses can escape host cells before the induction of lysis via release in extracellular vesicles (EVs). These nanosized EVs cloak the secreted virus particles in a host-derived membrane, which alters virus-host interactions that affect infection efficiency and antiviral immunity. Currently, little is known about the viral and host factors regulating this form of virus release. Here, we assessed the role of the encephalomyocarditis virus (EMCV) Leader protein, a ‘viral security protein’ that subverts the host antiviral response. EV release upon infection with wildtype virus or a Leader-deficient mutant was characterized at the single particle level using high-resolution flow cytometry. Inactivation of the Leader abolished EV induction during infection and strongly reduced EV-enclosed virus release. We demonstrate that the Leader promotes the release of virions within EVs by stimulating a secretory arm of autophagy. This newly discovered role of the EMCV Leader adds to the variety of mechanisms via which this protein affects virus-host interactions. Moreover, these data provide first evidence for a crucial role of a non-structural viral protein in the non-lytic release of picornaviruses via packaging in EVs. Picornaviruses can escape infected cells via packaging in extracellular vesicles (EVs). Here, van der Grein et al. show that the non-structural Leader protein of encephalomyocarditis virus (EMCV) promotes the release of EV-enclosed virus particles and provide evidence for a role of secretory autophagy in this process.
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影响因子：
64.8
作者：
Feng Z;Hensley L;McKnight KL;Hu F;Madden V;Ping L;Jeong SH;Walker C;Lanford RE;Lemon SM
通讯作者：
Lemon SM
影响因子：
15.1
作者：
Danzer KM;Kranich LR;Ruf WP;Cagsal-Getkin O;Winslow AR;Zhu L;Vanderburg CR;McLean PJ
通讯作者：
McLean PJ
影响因子：
64.5
作者：
Gee, Heon Yung;Noh, Shin Hye;Lee, Min Goo
通讯作者：
Lee, Min Goo
影响因子：
6.4
作者：
Das A;Hirai-Yuki A;González-López O;Rhein B;Moller-Tank S;Brouillette R;Hensley L;Misumi I;Lovell W;Cullen JM;Whitmire JK;Maury W;Lemon SM
通讯作者：
Lemon SM
影响因子：
6.7
作者：
Fu Y;Zhang L;Zhang F;Tang T;Zhou Q;Feng C;Jin Y;Wu Z
通讯作者：
Wu Z