β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway.
β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway.
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β-冠状病毒使用溶酶体而不是生物合成分泌途径进行出口。
DOI：
10.1016/j.cell.2020.10.039
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发表时间：
2020-12-10
期刊：
影响因子：
64.5
通讯作者：
Altan-Bonnet N
中科院分区：
文献类型：
--
作者：
Ghosh S;Dellibovi-Ragheb TA;Kerviel A;Pak E;Qiu Q;Fisher M;Takvorian PM;Bleck C;Hsu VW;Fehr AR;Perlman S;Achar SR;Straus MR;Whittaker GR;de Haan CAM;Kehrl J;Altan-Bonnet G;Altan-Bonnet N
β-冠状病毒是一个正链包膜RNA病毒家族，包括严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。关于它们的细胞进入和复制途径已经知道很多，但它们的出口模式仍然不确定。使用成像方法和病毒特异性报告基因，我们证明β-冠状病毒利用溶酶体运输外出，而不是其他包膜病毒更常用的生物合成分泌途径。这种非常规的排出受Arf样小GT3 Arl 8b调节，并且可以被Rab 7 GT3竞争性抑制剂CID 1067700阻断。β-冠状病毒的这种非裂解性释放导致溶酶体脱酸、溶酶体降解酶失活和抗原呈递途径破坏。β-冠状病毒诱导的利用溶酶体细胞器外出提供了对患者中观察到的细胞和免疫异常的见解，并提出了新的治疗方式。Ghosh等人提供证据表明，β-冠状病毒不使用包膜病毒通常使用的生物合成分泌途径离开感染细胞。相反，这些病毒通过Arl 8b依赖性溶酶体胞吐作用运输到溶酶体以进行非常规外出。它们的非溶解性释放导致溶酶体脱酸、溶酶体降解酶的失活和抗原呈递的破坏。
β-Coronaviruses are a family of positive-strand enveloped RNA viruses that includes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much is known regarding their cellular entry and replication pathways, but their mode of egress remains uncertain. Using imaging methodologies and virus-specific reporters, we demonstrate that β-coronaviruses utilize lysosomal trafficking for egress rather than the biosynthetic secretory pathway more commonly used by other enveloped viruses. This unconventional egress is regulated by the Arf-like small GTPase Arl8b and can be blocked by the Rab7 GTPase competitive inhibitor CID1067700. Such non-lytic release of β-coronaviruses results in lysosome deacidification, inactivation of lysosomal degradation enzymes, and disruption of antigen presentation pathways. β-Coronavirus-induced exploitation of lysosomal organelles for egress provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities. Ghosh et al. provide evidence that β-coronaviruses do not use the biosynthetic secretory pathway typically used by enveloped viruses to leave infected cells. Instead, these viruses traffic to lysosomes for unconventional egress by Arl8b-dependent lysosomal exocytosis. Their non-lytic release results in lysosome deacidification, inactivation of lysosomal degradation enzymes, and disruption of antigen presentation.
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影响因子：
30.5
作者：
Garcia-Beltran WF;Hölzemer A;Martrus G;Chung AW;Pacheco Y;Simoneau CR;Rucevic M;Lamothe-Molina PA;Pertel T;Kim TE;Dugan H;Alter G;Dechanet-Merville J;Jost S;Carrington M;Altfeld M
通讯作者：
Altfeld M
影响因子：
6.4
作者：
Castaño-Rodriguez C;Honrubia JM;Gutiérrez-Álvarez J;DeDiego ML;Nieto-Torres JL;Jimenez-Guardeño JM;Regla-Nava JA;Fernandez-Delgado R;Verdia-Báguena C;Queralt-Martín M;Kochan G;Perlman S;Aguilella VM;Sola I;Enjuanes L
通讯作者：
Enjuanes L
影响因子：
2.9
作者：
GRAHAM, JM;FORD, T;RICKWOOD, D
通讯作者：
RICKWOOD, D
DOI：
10.1074/jbc.ra118.001897
发表时间：
2018-07-27
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chu H;Chan CM;Zhang X;Wang Y;Yuan S;Zhou J;Au-Yeung RK;Sze KH;Yang D;Shuai H;Hou Y;Li C;Zhao X;Poon VK;Leung SP;Yeung ML;Yan J;Lu G;Jin DY;Gao GF;Chan JF;Yuen KY
通讯作者：
Yuen KY
影响因子：
4.8
作者：
de Bouteiller, O;Merck, E;Caux, C
通讯作者：
Caux, C