β-冠狀病毒使用溶酶體來輸出
作者:
小柯機器人發布時間:2020/10/28 15:18:17
美國國立衛生研究院Nihal Altan-Bonnet、Gregoire Altan-Bonnet等研究人員合作發現,β-冠狀病毒使用溶酶體來輸出,而非生物合成的分泌途徑。2020年10月27日,《細胞》雜誌在線發表了這項成果。
使用成像方法和病毒特異性報告基因,研究人員證明了β冠狀病毒利用溶酶體運輸進行輸出,而不是其他包膜病毒更常用的生物合成分泌途徑。這種非常規的輸出受到類似於Arf的小GTPase Arl8b調控,並且可以被Rab7 GTPase競爭性抑制劑CID1067700所阻斷。
β冠狀病毒的這種非裂解釋放導致溶酶體變鹼、溶酶體降解酶失活以及抗原呈遞途徑的破壞。β冠狀病毒引起的溶酶體壓榨為患者的細胞和免疫異常提供了見識,並提出了新的治療方法。
據介紹,β冠狀病毒是一類正鏈包裹的RNA病毒,包括SARS-CoV2。關於它們的進入細胞和複製途徑已了解很多,但是它們輸出的方式仍然不確定。
附:英文原文
Title: β-Coronaviruses use lysosomes for egress instead of the biosynthetic secretory pathway
Author: Sourish Ghosh, Teegan A. Dellibovi-Ragheb, Adeline Kerviel, Eowyn Pak, Qi Qiu, Matthew Fisher, Peter M. Takvorian, Christopher Bleck, Victor Hsu, Anthony R. Fehr, Stanley Perlman, Souraj R. Achar, Marco R. Straus, Gary R. Whittaker, Cornelis A.M. de Haan, John Kehrl, Gregoire Altan-Bonnet, Nihal Altan-Bonnet
Issue&Volume:
Abstract: β-Coronaviruses are a family of positive-strand enveloped RNA viruses that include the severe acute respiratory syndrome-CoV2 (SARS-CoV2). 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-Coronavirus results in lysosome deacidification, inactivation of lysosomal degradation enzymes and disruption of antigen presentation pathways. The βcoronavirus-induced exploitation of lysosomal organelles for egress provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.
DOI: 10.1016/j.cell.2020.10.039
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31446-X
Cell:《細胞》,創刊於1974年。隸屬於細胞出版社,最新IF:36.216