Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2.
Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2.
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DOI：
10.1038/s42003-021-02030-3
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发表时间：
2021-04-12
影响因子：
5.9
通讯作者：
Seshagiri S
中科院分区：
文献类型：
--
作者：
Suryamohan K;Diwanji D;Stawiski EW;Gupta R;Miersch S;Liu J;Chen C;Jiang YP;Fellouse FA;Sathirapongsasuti JF;Albers PK;Deepak T;Saberianfar R;Ratan A;Washburn G;Mis M;Santhosh D;Somasekar S;Hiranjith GH;Vargas D;Mohan S;Phalke S;Kuriakose B;Antony A;Ustav M Jr;Schuster SC;Sidhu S;Junutula JR;Jura N;Seshagiri S
COVID-19是由一种名为SARS-CoV-2的新型冠状病毒引起的呼吸道疾病。病毒刺突（S）蛋白与人血管紧张素转换酶2（ACE 2）受体结合，以比SARS-CoV S蛋白高约10-15倍的亲和力侵入宿主细胞，使其具有高度感染性。在这里，我们评估了ACE 2多态性是否可以通过影响这种相互作用来改变宿主对SARS-CoV-2的易感性。我们分析了来自公共基因组数据集的超过290，000个代表超过400个人群的样本，并鉴定了多种ACE 2蛋白质改变变体。使用报告的结构数据，我们确定了可能影响病毒-宿主相互作用从而改变宿主易感性的天然ACE 2变体。这些包括预测增加易感性的变体S19 P、I21 V、E23 K、K26 R、T27 A、N64 K、T92 I、Q102 P和H378 R，而变体K31 R、N33 I、H34 R、E35 K、E37 K、D38 V、Y50 F、N51 S、M62 V、K68 E、F72 V、Y83 H、G326 E、G352 V、D355 N、预测Q388 L和D509 Y是显示与S蛋白结合降低的保护性变体。使用生物化学测定，我们证实，与野生型ACE 2相比，K31 R和E37 K对S蛋白的亲和力降低，K26 R和T92 I变体对S蛋白的亲和力增加。与此一致，可溶性ACE 2 K26 R和T92 I在阻断S蛋白假型病毒进入方面更有效，表明ACE 2变体可以调节对SARS-CoV-2的易感性。Suryamohan、Diwanji、Stawiski等人鉴定了预测会改变病毒-宿主相互作用的天然ACE 2变体。他们发现，与野生型ACE 2相比，可溶性ACE 2 K26 R和T92 I变体在阻断SARS-CoV-2 S蛋白假型病毒进入方面更有效。这项研究表明ACE 2变异体可能调节宿主对SARS-CoV-2的易感性。
COVID-19 is a respiratory illness caused by a novel coronavirus called SARS-CoV-2. The viral spike (S) protein engages the human angiotensin-converting enzyme 2 (ACE2) receptor to invade host cells with ~10–15-fold higher affinity compared to SARS-CoV S-protein, making it highly infectious. Here, we assessed if ACE2 polymorphisms can alter host susceptibility to SARS-CoV-2 by affecting this interaction. We analyzed over 290,000 samples representing >400 population groups from public genomic datasets and identified multiple ACE2 protein-altering variants. Using reported structural data, we identified natural ACE2 variants that could potentially affect virus–host interaction and thereby alter host susceptibility. These include variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R that were predicted to increase susceptibility, while variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y were predicted to be protective variants that show decreased binding to S-protein. Using biochemical assays, we confirmed that K31R and E37K had decreased affinity, and K26R and T92I variants showed increased affinity for S-protein when compared to wildtype ACE2. Consistent with this, soluble ACE2 K26R and T92I were more effective in blocking entry of S-protein pseudotyped virus suggesting that ACE2 variants can modulate susceptibility to SARS-CoV-2. Suryamohan, Diwanji, Stawiski et al. identify natural ACE2 variants that are predicted to alter virus–host interactions. They find that soluble ACE2 K26R and T92I variants are more effective in blocking the entry of SARS-CoV-2 S-protein pseudotyped virus, compared to wild-type ACE2. This study suggests that ACE2 variants may modulate the host susceptibility to SARS-CoV-2.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
168.9
作者：
Chan, Jasper Fuk-Woo;Yuan, Shuofeng;Yuen, Kwok-Yung
通讯作者：
Yuen, Kwok-Yung
影响因子：
5.2
作者：
Benetti, Elisa;Tita, Rossella;Pinto, Anna Maria
通讯作者：
Pinto, Anna Maria
DOI：
10.1126/science.abc0870
发表时间：
2020-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chan KK;Dorosky D;Sharma P;Abbasi SA;Dye JM;Kranz DM;Herbert AS;Procko E
通讯作者：
Procko E
影响因子：
9.8
作者：
Albers, Patrick K.;McVean, Gil
通讯作者：
McVean, Gil