Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection.
Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection.
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DOI：
10.1038/s41588-022-01131-x
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发表时间：
2022-08
期刊：
影响因子：
30.8
通讯作者：
Hsu, Patrick D.
中科院分区：
文献类型：
--
作者：
Biering, Scott B.;Sarnik, Sylvia A.;Wang, Eleanor;Zengel, James R.;Leist, Sarah R.;Schafer, Alexandra;Sathyan, Varun;Hawkins, Padraig;Okuda, Kenichi;Tau, Cyrus;Jangid, Aditya R.;Duffy, Connor, V;Wei, Jin;Gilmore, Rodney C.;Alfajaro, Mia Madel;Strine, Madison S.;Nguyenla, Xammy;Van Dis, Erik;Catamura, Carmelle;Yamashiro, Livia H.;Belk, Julia A.;Begeman, Adam;Stark, Jessica C.;Shon, D. Judy;Fox, Douglas M.;Ezzatpour, Shahrzad;Huang, Emily;Olegario, Nico;Rustagi, Arjun;Volmer, Allison S.;Livraghi-Butrico, Alessandra;Wehri, Eddie;Behringer, Richard R.;Cheon, Dong-Joo;Schaletzky, Julia;Aguilar, Hector C.;Puschnik, Andreas S.;Button, Brian;Pinsky, Benjamin A.;Blish, Catherine A.;Baric, Ralph S.;O'Neal, Wanda K.;Bertozzi, Carolyn R.;Wilen, Craig B.;Boucher, Richard C.;Carette, Jan E.;Stanley, Sarah A.;Harris, Eva;Konermann, Silvana;Hsu, Patrick D.
严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）在感染个体中引起一系列症状，从轻度呼吸道疾病到急性呼吸窘迫综合征。系统了解影响病毒感染的宿主因素对于阐明SARS-CoV-2-宿主相互作用和2019冠状病毒病（COVID-19）的进展至关重要。在这里，我们在内源性表达SARS-CoV-2进入因子ACE 2和TMPRSS 2的人肺上皮细胞中进行了全基因组CRISPR敲除和激活筛选。我们发现了前病毒和抗病毒因子在高度相互关联的宿主途径，包括网格蛋白转运，炎症信号，细胞周期调控，转录和表观遗传调控。我们进一步鉴定了粘蛋白，一个高分子量糖蛋白家族，作为一个突出的病毒限制性网络，在体外和小鼠模型中抑制SARS-CoV-2感染。这些粘蛋白还抑制多种呼吸道病毒的感染。SARS-CoV-2宿主因子的这种功能景观为新的宿主导向疗法提供了生理学相关的起点，并突出了气道粘蛋白作为宿主防御机制。在内源性表达SARS-CoV-2进入因子ACE 2和TMPRSS 2的人肺上皮细胞中进行的全基因组CRISPR敲除和激活筛选将粘蛋白鉴定为限制病毒感染的关键宿主因子。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of host factors influencing viral infection is critical to elucidate SARS-CoV-2–host interactions and the progression of Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. We uncovered proviral and antiviral factors across highly interconnected host pathways, including clathrin transport, inflammatory signaling, cell-cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high molecular weight glycoproteins, as a prominent viral restriction network that inhibits SARS-CoV-2 infection in vitro and in murine models. These mucins also inhibit infection of diverse respiratory viruses. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and highlights airway mucins as a host defense mechanism. Genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2 identify mucins as key host factors restricting viral infection.
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DOI：
10.1007/978-1-4939-0888-2_10
发表时间：
2014
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Bagga S;Bouchard MJ
通讯作者：
Bouchard MJ
DOI：
10.1083/jcb.131.6.1623
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bennett KL;Modrell B;Greenfield B;Bartolazzi A;Stamenkovic I;Peach R;Jackson DG;Spring F;Aruffo A
通讯作者：
Aruffo A
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：
4.6
作者：
Haston, CK;Cory, S;Hallett, MT
通讯作者：
Hallett, MT
影响因子：
32.4
作者：
Hoagland DA;Møller R;Uhl SA;Oishi K;Frere J;Golynker I;Horiuchi S;Panis M;Blanco-Melo D;Sachs D;Arkun K;Lim JK;tenOever BR
通讯作者：
tenOever BR