Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq
Author:
Sunshine SaraORCID, Puschnik Andreas S.ORCID, Replogle Joseph M.ORCID, Laurie Matthew T.ORCID, Liu JaminORCID, Zha Beth ShoshanaORCID, Nuñez James K.ORCID, Byrum Janie R.ORCID, McMorrow Aidan H.ORCID, Frieman Matthew B.ORCID, Winkler JulianeORCID, Qiu XiaojieORCID, Rosenberg Oren S.ORCID, Leonetti Manuel D.ORCID, Ye Chun JimmieORCID, Weissman Jonathan S.ORCID, DeRisi Joseph L.ORCID, Hein Marco Y.ORCID
Abstract
Numerous host factors of SARS-CoV-2 have been identified by screening approaches, but delineating their molecular roles during infection and whether they can be targeted for antiviral intervention remains a challenge. Here we use Perturb-seq, a single-cell CRISPR screening approach, to investigate how CRISPR interference of host factors changes the course of SARS-CoV-2 infection and the host response in human lung epithelial cells. Our data reveal two classes of host factors with pronounced phenotypes: factors required for the response to interferon and factors required for entry or early infection. Among the latter, we have characterized 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 high-throughput functional validation of host factors of SARS-CoV-2 and describes their roles during viral infection in both infected and bystander cells.
Publisher
Cold Spring Harbor Laboratory
Reference72 articles.
1. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing 2. D. E. Gordon , J. Hiatt , M. Bouhaddou , V. V. Rezelj , S. Ulferts , H. Braberg , A. S. Jureka , K. Obernier , J. Z. Guo , J. Batra , R. M. Kaake , A. R. Weckstein , T. W. Owens , M. Gupta , S. Pourmal , E. W. Titus , M. Cakir , M. Soucheray , M. McGregor , Z. Cakir , G. Jang , M. J. O’Meara , T. A. Tummino , Z. Zhang , H. Foussard , A. Rojc , Y. Zhou , D. Kuchenov , R. Hüttenhain , J. Xu , M. Eckhardt , D. L. Swaney , J. M. Fabius , M. Ummadi , B. Tutuncuoglu , U. Rathore , M. Modak , P. Haas , K. M. Haas , Z. Z. C. Naing , E. H. Pulido , Y. Shi , I. Barrio-Hernandez , D. Memon , E. Petsalaki , A. Dunham , M. C. Marrero , D. Burke , C. Koh , T. Vallet , J. A. Silvas , C. M. Azumaya , C. Billesbølle , A. F. Brilot , M. G. Campbell , A. Diallo , M. S. Dickinson , D. Diwanji , N. Herrera , N. Hoppe , H. T. Kratochvil , Y. Liu , G. E. Merz , M. Moritz , H. C. Nguyen , C. Nowotny , C. Puchades , A. N. Rizo , U. Schulze-Gahmen , A. M. Smith , M. Sun , I. D. Young , J. Zhao , D. Asarnow , J. Biel , A. Bowen , J. R. Braxton , J. Chen , C. M. Chio , U. S. Chio , I. Deshpande , L. Doan , B. Faust , S. Flores , M. Jin , K. Kim , V. L. Lam , F. Li , J. Li , Y.-L. Li , Y. Li , X. Liu , M. Lo , K. E. Lopez , A. A. Melo , F. R. Moss , 3rd, P. Nguyen , J. Paulino , K. I. Pawar , J. K. Peters , T. H. Pospiech, Jr , M. Safari , S. Sangwan , K. Schaefer , P. V. Thomas , A. C. Thwin , R. Trenker , E. Tse , T. K. M. Tsui , F. Wang , N. Whitis , Z. Yu , K. Zhang , Y. Zhang , F. Zhou , D. Saltzberg , QCRG Structural Biology Consortium, A. J. Hodder , A. S. Shun-Shion , D. M. Williams , K. M. White , R. Rosales , T. Kehrer , L. Miorin , E. Moreno , A. H. Patel , S. Rihn , M. M. Khalid , A. Vallejo-Gracia , P. Fozouni , C. R. Simoneau , T. L. Roth , D. Wu , M. A. Karim , M. Ghoussaini , I. Dunham , F. Berardi , S. Weigang , M. Chazal , J. Park , J. Logue , M. McGrath , S. Weston , R. Haupt , C. J. Hastie , M. Elliott , F. Brown , K. A. Burness , E. Reid , M. Dorward , C. Johnson , S. G. Wilkinson , A. Geyer , D. M. Giesel , C. Baillie , S. Raggett , H. Leech , R. Toth , N. Goodman , K. C. Keough , A. L. Lind , Zoonomia Consortium, R. J. Klesh , K. R. Hemphill , J. Carlson-Stevermer , J. Oki , K. Holden , T. Maures , K. S. Pollard , A. Sali , D. A. Agard , Y. Cheng , J. S. Fraser , A. Frost , N. Jura , T. Kortemme , A. Manglik , D. R. Southworth , R. M. Stroud , D. R. Alessi , P. Davies , M. B. Frieman , T. Ideker , C. Abate , N. Jouvenet , G. Kochs , B. Shoichet , M. Ott , M. Palmarini , K. M. Shokat , A. García-Sastre , J. A. Rassen , R. Grosse , O. S. Rosenberg , K. A. Verba , C. F. Basler , M. Vignuzzi , A. A. Peden , P. Beltrao , and N. J. Krogan . Comparative hostcoronavirus protein interaction networks reveal pan-viral disease mechanisms. Science, 370(6521), December 2020. 3. The SARS-CoV-2 RNA–protein interactome in infected human cells;Nature Microbiology,2021 4. Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV;Nature,2021 5. Genome-Scale identification of SARS-CoV-2 and pan-coronavirus host factor networks;Cell,2021
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|