文献类型： 外文期刊

作者： Yin, Xin ¹ ; Pu, Yuan ² ; Yuan, Shuofeng ³ ; Pache, Lars ⁴ ; Churas, Christopher ⁵ ; Weston, Stuart ⁶ ; Riva, Laura ⁷ ; Simons, Lacy M. ⁸ ; Cisneros, William J. ⁸ ; Clausen, Thomas ¹⁰ ; Biddle, Grace ⁶ ; Doss-Gollin, Simon ⁶ ; Deming, Meagan ⁶ ; De Jesus, Paul D. ² ; Kim, Ha Na ¹¹ ; Fuentes, Daniel ² ; Whitelock, John M. ¹¹ ; Esko, Jeffrey D. ¹⁰ ; Lord, Megan S. ¹¹ ; Mena, Ignacio ² ; Garcia-Sastre, Adolfo ¹² ; Hultquist, Judd F. ⁸ ; Frieman, Matthew B. ⁶ ; Ideker, Trey ⁵ ; Pratt, Dexter ⁵ ; Martin-Sancho, Laura ¹⁹ ; Chanda, Sumit K. ² ;

作者机构： 1.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Harbin, Peoples R China

2.Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA USA

3.Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Hong Kong, Peoples R China

4.Sanford Burnham Prebys Med Discovery Inst, NCI Designated Canc Ctr, La Jolla, CA USA

5.Univ Calif San Diego, Dept Med, La Jolla, CA USA

6.Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD USA

7.Calibr Skaggs Scripps Res Inst, La Jolla, CA USA

8.Northwestern Univ, Feinberg Sch Med, Dept Med, Div Infect Dis, Chicago, IL USA

9.Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Div Infect Dis, Chicago, IL USA

10.Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA USA

11.Univ New South Wales, Grad Sch Biomed Engn, Sydney, Australia

12.Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY USA

13.Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY USA

14.Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY USA

15.Icahn Sch Med Mt Sinai, Tisch Inst, New York, NY USA

16.Icahn Sch Med Mt Sinai, Dept Pathol Mol & Cell Based Med, New York, NY USA

17.Icahn Sch Med Mt Sinai, Icahn Genom Inst, New York, NY USA

18.Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA USA

19.Imperial Coll London, Dept Infect Dis, London, England

期刊名称：PLOS BIOLOGY （ 影响因子：7.2； 五年影响因子：7.7 ）

ISSN： 1544-9173

年卷期： 2025 年 23 卷 6 期

页码：

收录情况： SCI

摘要： Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously reported SARS-CoV-2 host dependency factors, most of these approaches relied on utilizing pooled genome-scale CRISPR libraries, which are biased toward the discovery of host proteins impacting early stages of viral replication. To identify host factors involved throughout the SARS-CoV-2 infectious cycle, we conducted an arrayed genome-scale siRNA screen. Resulting data were integrated with published functional screens and proteomics data to reveal (i) common pathways that were identified in all OMICs datasets-including regulation of Wnt signaling and gap junctions, (ii) pathways uniquely identified in this screen-including NADH oxidation, or (iii) pathways supported by this screen and proteomics data but not published functional screens-including arachionate production and MAPK signaling. The identified proviral host factors were mapped into the SARS-CoV-2 infectious cycle, including 32 proteins that were determined to impact viral replication and 27 impacting late stages of infection, respectively. Additionally, a subset of proteins was tested across other coronaviruses revealing a subset of proviral factors that were conserved across pandemic SARS-CoV-2, epidemic SARS-CoV-1 and MERS-CoV, and the seasonal coronavirus OC43-CoV. Further studies illuminated a role for the heparan sulfate proteoglycan perlecan in SARS-CoV-2 viral entry and found that inhibition of the non-canonical NF-kB pathway through targeting of BIRC2 restricts SARS-CoV-2 replication both in vitro and in vivo. These studies provide critical insight into the landscape of virus-host interactions driving SARS-CoV-2 replication as well as valuable targets for host-directed antivirals.