AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells.
AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells.
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AXL 是 SARS-CoV-2 的候选受体，可促进肺和支气管上皮细胞的感染
DOI：
10.1038/s41422-020-00460-y
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发表时间：
2021-03
期刊：
影响因子：
44.1
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Wang S;Qiu Z;Hou Y;Deng X;Xu W;Zheng T;Wu P;Xie S;Bian W;Zhang C;Sun Z;Liu K;Shan C;Lin A;Jiang S;Xie Y;Zhou Q;Lu L;Huang J;Li X
当前的2019冠状病毒病（COVID-19）大流行对全球公共卫生构成挑战。病毒病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）通过其刺突（S）糖蛋白与宿主受体ACE 2结合，介导膜融合和病毒进入。虽然ACE 2作为SARS-CoV-2受体的作用是明确的，但研究表明ACE 2在各种人体组织中的表达极低，特别是在呼吸道中。因此，可能存在促进SARS-CoV-2进入呼吸系统细胞的其他宿主受体和/或辅助受体。本研究中，我们发现酪氨酸蛋白激酶受体UFO（AXL）与SARS-CoV-2S的N端结构域特异性相互作用。使用SARS-CoV-2病毒假型和真实的SARS-CoV-2，我们发现在HEK 293 T细胞中过表达AXL与过表达ACE 2一样有效地促进SARS-CoV-2进入，而敲除AXL显著降低了H1299肺细胞和人原代肺上皮细胞中的SARS-CoV-2感染。可溶性人重组AXL阻断SARS-CoV-2在表达高水平AXL的细胞中的感染。AXL表达水平与COVID-19患者支气管肺泡灌洗液细胞中SARS-CoV-2 S水平密切相关。综上所述，我们的研究结果表明，AXL是一个新的候选受体SARS冠状病毒2，这可能在促进人类呼吸系统的病毒感染中发挥重要作用，并表明它是一个潜在的目标，为未来的临床干预策略。
The current coronavirus disease 2019 (COVID-19) pandemic presents a global public health challenge. The viral pathogen responsible, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the host receptor ACE2 through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. Although the role of ACE2 as a receptor for SARS-CoV-2 is clear, studies have shown that ACE2 expression is extremely low in various human tissues, especially in the respiratory tract. Thus, other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system may exist. In this study, we found that the tyrosine-protein kinase receptor UFO (AXL) specifically interacts with the N-terminal domain of SARS-CoV-2 S. Using both a SARS-CoV-2 virus pseudotype and authentic SARS-CoV-2, we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently as overexpression of ACE2, while knocking out AXL significantly reduces SARS-CoV-2 infection in H1299 pulmonary cells and in human primary lung epithelial cells. Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL. The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients. Taken together, our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role in promoting viral infection of the human respiratory system and indicate that it is a potential target for future clinical intervention strategies.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
64.5
作者：
Daniloski Z;Jordan TX;Wessels HH;Hoagland DA;Kasela S;Legut M;Maniatis S;Mimitou EP;Lu L;Geller E;Danziger O;Rosenberg BR;Phatnani H;Smibert P;Lappalainen T;tenOever BR;Sanjana NE
通讯作者：
Sanjana NE
影响因子：
56.9
作者：
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
6.7
作者：
Jemielity S;Wang JJ;Chan YK;Ahmed AA;Li W;Monahan S;Bu X;Farzan M;Freeman GJ;Umetsu DT;Dekruyff RH;Choe H
通讯作者：
Choe H