CLN7/MFSD8 may be an important factor for SARS-CoV-2 cell entry.

CLN7/MFSD8 may be an important factor for SARS-CoV-2 cell entry.
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DOI:
10.1016/j.isci.2022.105082
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发表时间:
2022-10-21
期刊:
影响因子:
5.8
通讯作者:
Reichold, Markus
Reichold, Markus
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Heinl, Elena -Sofia;Lorenz, Sebastian;Schmidt, Barbara;Laqtom, Nouf Nasser M.;Mazzulli, Joseph R.;Francelle, Laetitia;Yu, Timothy W.;Greenberg, Benjamin;Storch, Stephan;Tegtmeier, Ines;Othmen, Helga;Maurer, Katja;Steinfurth, Malin;Witzgall, Ralph;Milenkovic, Vladimir;Wetzel, Christian H.;Reichold, Markus

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SARS-CoV-2病毒已经引发了一场全球性的大流行。根据BioGrid数据库,CLN 7(MFSD 8)被认为与几种病毒蛋白相互作用。这项工作的目的是研究CLN 7在感染过程中的可能参与。与野生型细胞相比,在CLN 7缺陷型HEK 293 T细胞系上的实验表现出90%的病毒载量降低。这一观察结果可能与CLN 7 ko细胞在其细胞膜中具有显著降低的GM 1含量的发现有关。GM 1在脂筏中高度富集,脂筏被认为在SARS-CoV-2感染中起重要作用。相反,CLN 7的过表达导致病毒载量的增加。本研究提供了CLN 7参与SARS-CoV-2感染的证据。这使其成为抗COVID-19药物开发的潜在药理学靶点。此外,它还提供了对CLN 7生理功能的深入了解,其中仍然知之甚少。CLN 7基因敲除可保护细胞免受SARS-CoV-2感染CLN 7基因敲除导致细胞GM 1含量大幅降低GM 1含量降低可能导致CLN 7缺陷细胞中脂筏功能降低病毒学;细胞生物学
The SARS-CoV-2 virus has triggered a worldwide pandemic. According to the BioGrid database, CLN7 (MFSD8) is thought to interact with several viral proteins. The aim of this work was to investigate a possible involvement of CLN7 in the infection process. Experiments on a CLN7-deficient HEK293T cell line exhibited a 90% reduced viral load compared to wild-type cells. This observation may be linked to the finding that CLN7 ko cells have a significantly reduced GM1 content in their cell membrane. GM1 is found highly enriched in lipid rafts, which are thought to play an important role in SARS-CoV-2 infection. In contrast, overexpression of CLN7 led to an increase in viral load. This study provides evidence that CLN7 is involved in SARS-CoV-2 infection. This makes it a potential pharmacological target for drug development against COVID-19. Furthermore, it provides insights into the physiological function of CLN7 where still only little is known about. CLN7 knockout protects cells from SARS-CoV-2 infection CLN7 knockout leads to a strong reduction of cellular GM1 content A reduced GM1 content might lead to a reduced lipid raft function in CLN7-deficient cells Virology; Cell biology
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