Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq.
Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq.
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DOI：
10.1038/s41467-023-41788-4
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发表时间：
2023-10-06
影响因子：
16.6
通讯作者：
Hein, Marco Y.
中科院分区：
文献类型：
--
作者：
Sunshine, Sara;Puschnik, Andreas S.;Replogle, Joseph M.;Laurie, Matthew T.;Liu, Jamin;Zha, Beth Shoshana;Nunez, James K.;Byrum, Janie R.;Mcmorrow, Aidan H.;Frieman, Matthew B.;Winkler, Juliane;Qiu, Xiaojie;Rosenberg, Oren S.;Leonetti, Manuel D.;Ye, Chun Jimmie;Weissman, Jonathan S.;Derisi, Joseph L.;Hein, Marco Y.
基因组和蛋白质组筛选已经确定了SARS-CoV-2的许多宿主因子，但有效地描绘它们在感染过程中的分子作用仍然是一个挑战。在这里，我们使用Perturb-seq，将遗传扰动与单细胞读数相结合，研究宿主因子的失活如何改变SARS-CoV-2感染的过程和人肺上皮细胞中的宿主反应。我们的高维数据解决了复杂的表型，如感染阶段的变化和干扰素反应的调节。然而，只有一小部分宿主因子在扰动后表现出这种表型。我们进一步鉴定了NF-κB抑制剂IκBα（NF KBIA）以及翻译因子EIF 4 E2和EIF 4 H作为在感染早期起作用的强宿主依赖性因子。总的来说，我们的研究提供了大量的并行功能表征的宿主因子的SARS-CoV-2，并定量定义其在病毒感染和旁观者细胞中的作用。Sunshine等人使用Perturb-seq研究SARS-CoV-2的宿主依赖性，通过遗传灭活宿主因子，并通过单细胞测序监测感染过程，表征全局宿主表型。他们将NFKBIA、EIF 4 E2和EIF 4 H确定为强宿主依赖性因子。
Genomic and proteomic screens have identified numerous host factors of SARS-CoV-2, but efficient delineation of their molecular roles during infection remains a challenge. Here we use Perturb-seq, combining genetic perturbations with a single-cell readout, to investigate how inactivation of host factors changes the course of SARS-CoV-2 infection and the host response in human lung epithelial cells. Our high-dimensional data resolve complex phenotypes such as shifts in the stages of infection and modulations of the interferon response. However, only a small percentage of host factors showed such phenotypes upon perturbation. We further identified the NF-κB inhibitor IκBα (NFKBIA), as well as the translation factors EIF4E2 and EIF4H as strong host dependency factors acting early in infection. Overall, our study provides massively parallel functional characterization of host factors of SARS-CoV-2 and quantitatively defines their roles both in virus-infected and bystander cells. Sunshine et al. use Perturb-seq to study host dependencies of SARS-CoV-2 by inactivating host factors genetically and monitoring the course of infection by single-cell sequencing, characterizing global host phenotypes. They identified NFKBIA, EIF4E2 and EIF4H as strong host dependency factors.
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影响因子：
64.5
作者：
Jaitin, Diego Adhemar;Weiner, Assaf;Amit, Ido
通讯作者：
Amit, Ido
DOI：
10.1126/science.abe9403
发表时间：
2020-12-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gordon DE;Hiatt J;Bouhaddou M;Rezelj VV;Ulferts S;Braberg H;Jureka AS;Obernier K;Guo JZ;Batra J;Kaake RM;Weckstein AR;Owens TW;Gupta M;Pourmal S;Titus EW;Cakir M;Soucheray M;McGregor M;Cakir Z;Jang G;O'Meara MJ;Tummino TA;Zhang Z;Foussard H;Rojc A;Zhou Y;Kuchenov D;Hüttenhain R;Xu J;Eckhardt M;Swaney DL;Fabius JM;Ummadi M;Tutuncuoglu B;Rathore U;Modak M;Haas P;Haas KM;Naing ZZC;Pulido EH;Shi Y;Barrio-Hernandez I;Memon D;Petsalaki E;Dunham A;Marrero MC;Burke D;Koh C;Vallet T;Silvas JA;Azumaya CM;Billesbølle C;Brilot AF;Campbell MG;Diallo A;Dickinson MS;Diwanji D;Herrera N;Hoppe N;Kratochvil HT;Liu Y;Merz GE;Moritz M;Nguyen HC;Nowotny C;Puchades C;Rizo AN;Schulze-Gahmen U;Smith AM;Sun M;Young ID;Zhao J;Asarnow D;Biel J;Bowen A;Braxton JR;Chen J;Chio CM;Chio US;Deshpande I;Doan L;Faust B;Flores S;Jin M;Kim K;Lam VL;Li F;Li J;Li YL;Li Y;Liu X;Lo M;Lopez KE;Melo AA;Moss FR 3rd;Nguyen P;Paulino J;Pawar KI;Peters JK;Pospiech TH Jr;Safari M;Sangwan S;Schaefer K;Thomas PV;Thwin AC;Trenker R;Tse E;Tsui TKM;Wang F;Whitis N;Yu Z;Zhang K;Zhang Y;Zhou F;Saltzberg D;QCRG Structural Biology Consortium;Hodder AJ;Shun-Shion AS;Williams DM;White KM;Rosales R;Kehrer T;Miorin L;Moreno E;Patel AH;Rihn S;Khalid MM;Vallejo-Gracia A;Fozouni P;Simoneau CR;Roth TL;Wu D;Karim MA;Ghoussaini M;Dunham I;Berardi F;Weigang S;Chazal M;Park J;Logue J;McGrath M;Weston S;Haupt R;Hastie CJ;Elliott M;Brown F;Burness KA;Reid E;Dorward M;Johnson C;Wilkinson SG;Geyer A;Giesel DM;Baillie C;Raggett S;Leech H;Toth R;Goodman N;Keough KC;Lind AL;Zoonomia Consortium;Klesh RJ;Hemphill KR;Carlson-Stevermer J;Oki J;Holden K;Maures T;Pollard KS;Sali A;Agard DA;Cheng Y;Fraser JS;Frost A;Jura N;Kortemme T;Manglik A;Southworth DR;Stroud RM;Alessi DR;Davies P;Frieman MB;Ideker T;Abate C;Jouvenet N;Kochs G;Shoichet B;Ott M;Palmarini M;Shokat KM;García-Sastre A;Rassen JA;Grosse R;Rosenberg OS;Verba KA;Basler CF;Vignuzzi M;Peden AA;Beltrao P;Krogan NJ
通讯作者：
Krogan NJ
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：
64.5
作者：
Feldman, David;Singh, Avtar;Blainey, Paul C.
通讯作者：
Blainey, Paul C.
影响因子：
30.3
作者：
Hoffmann HH;Sánchez-Rivera FJ;Schneider WM;Luna JM;Soto-Feliciano YM;Ashbrook AW;Le Pen J;Leal AA;Ricardo-Lax I;Michailidis E;Hao Y;Stenzel AF;Peace A;Zuber J;Allis CD;Lowe SW;MacDonald MR;Poirier JT;Rice CM
通讯作者：
Rice CM