Exocyst Complex Component 2 is a Potential Host Factor for SARS-CoV-2 Infection

Overview

Journal iScience

Publisher Cell Press

Date 2022 Oct 31

PMID 36310645

Authors

Renxing Yi

Rina Hashimoto

Ayaka Sakamoto

Yasufumi Matsumura

Miki Nagao

Kazutoshi Takahashi

Kazuo Takayama

Affiliations

Soon will be listed here.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an epidemic and spread rapidly all over the world. Because the analysis of host factors other than receptors and proteases has not been sufficiently performed, we attempted to identify and characterize host factors essential for SARS-CoV-2 infection using iPS cells and airway organoids (AO). Based on previous CRISPR screening and RNA-seq data, we found that exocyst complex component 2 (EXOC2) is one important host factor for SARS-CoV-2 infection. The intracellular SARS-CoV-2 nucleocapsid (N) expression level was decreased to 3.7% and the virus copy number in cell culture medium was decreased to 1.6% by EXOC2 knockdown. Consistently, immunostaining results showed that N protein-positive cells were significantly decreased by EXOC2 knockdown. We also found that EXOC2 knockdown downregulates SARS-CoV-2 infection by regulating IFNW1 expression. In conclusion, controlling the EXOC2 expression level may prevent SARS-CoV-2 infection and deserves further study.

Citing Articles

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References

Hoffmann M, Kleine-Weber H, Pohlmann S . A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells. Mol Cell. 2020; 78(4):779-784.e5. PMC: 7194065. DOI: 10.1016/j.molcel.2020.04.022. View

Wang R, Simoneau C, Kulsuptrakul J, Bouhaddou M, Travisano K, Hayashi J . Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses. Cell. 2020; 184(1):106-119.e14. PMC: 7723770. DOI: 10.1016/j.cell.2020.12.004. View

Mandegar M, Huebsch N, Frolov E, Shin E, Truong A, Olvera M . CRISPR Interference Efficiently Induces Specific and Reversible Gene Silencing in Human iPSCs. Cell Stem Cell. 2016; 18(4):541-53. PMC: 4830697. DOI: 10.1016/j.stem.2016.01.022. View

Zaman A, Wu X, Lemoff A, Yadavalli S, Lee J, Wang C . Exocyst protein subnetworks integrate Hippo and mTOR signaling to promote virus detection and cancer. Cell Rep. 2021; 36(5):109491. PMC: 8383154. DOI: 10.1016/j.celrep.2021.109491. View

Larson M, Gilbert L, Wang X, Lim W, Weissman J, Qi L . CRISPR interference (CRISPRi) for sequence-specific control of gene expression. Nat Protoc. 2013; 8(11):2180-96. PMC: 3922765. DOI: 10.1038/nprot.2013.132. View

Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I . Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci U S A. 2020; 117(13):7001-7003. PMC: 7132130. DOI: 10.1073/pnas.2002589117. View

Uhm M, Bazuine M, Zhao P, Chiang S, Xiong T, Karunanithi S . Phosphorylation of the exocyst protein Exo84 by TBK1 promotes insulin-stimulated GLUT4 trafficking. Sci Signal. 2017; 10(471). DOI: 10.1126/scisignal.aah5085. View

Wei J, Alfajaro M, DeWeirdt P, Hanna R, Lu-Culligan W, Cai W . Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection. Cell. 2020; 184(1):76-91.e13. PMC: 7574718. DOI: 10.1016/j.cell.2020.10.028. View

Schneider W, Luna J, Hoffmann H, Sanchez-Rivera F, Leal A, Ashbrook A . Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks. Cell. 2020; 184(1):120-132.e14. PMC: 7796900. DOI: 10.1016/j.cell.2020.12.006. View

10.

Horlbeck M, Gilbert L, Villalta J, Adamson B, Pak R, Chen Y . Compact and highly active next-generation libraries for CRISPR-mediated gene repression and activation. Elife. 2016; 5. PMC: 5094855. DOI: 10.7554/eLife.19760. View

11.

Jansens R, Tishchenko A, Favoreel H . Bridging the Gap: Virus Long-Distance Spread via Tunneling Nanotubes. J Virol. 2020; 94(8). PMC: 7108841. DOI: 10.1128/JVI.02120-19. View

12.

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S . SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-280.e8. PMC: 7102627. DOI: 10.1016/j.cell.2020.02.052. View

13.

Chien Y, Kim S, Bumeister R, Loo Y, Kwon S, Johnson C . RalB GTPase-mediated activation of the IkappaB family kinase TBK1 couples innate immune signaling to tumor cell survival. Cell. 2006; 127(1):157-70. DOI: 10.1016/j.cell.2006.08.034. View

14.

Sano E, Deguchi S, Sakamoto A, Mimura N, Hirabayashi A, Muramoto Y . Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells. iScience. 2021; 24(5):102428. PMC: 8051014. DOI: 10.1016/j.isci.2021.102428. View

15.

Flynn R, Belk J, Qi Y, Yasumoto Y, Wei J, Alfajaro M . Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021; 184(9):2394-2411.e16. PMC: 7951565. DOI: 10.1016/j.cell.2021.03.012. View

16.

Marzo L, Gousset K, Zurzolo C . Multifaceted roles of tunneling nanotubes in intercellular communication. Front Physiol. 2012; 3:72. PMC: 3322526. DOI: 10.3389/fphys.2012.00072. View

17.

Zhu Y, Feng F, Hu G, Wang Y, Yu Y, Zhu Y . A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry. Nat Commun. 2021; 12(1):961. PMC: 7878750. DOI: 10.1038/s41467-021-21213-4. View

18.

Wen Z, Zhang Y, Lin Z, Shi K, Jiu Y . Cytoskeleton-a crucial key in host cell for coronavirus infection. J Mol Cell Biol. 2020; 12(12):968-979. PMC: 7454755. DOI: 10.1093/jmcb/mjaa042. View

19.

Hashimoto R, Sakamoto A, Deguchi S, Yi R, Sano E, Hotta A . Dual inhibition of TMPRSS2 and Cathepsin Bprevents SARS-CoV-2 infection in iPS cells. Mol Ther Nucleic Acids. 2021; 26:1107-1114. PMC: 8527102. DOI: 10.1016/j.omtn.2021.10.016. View

20.

Simicek M, Lievens S, Laga M, Guzenko D, Aushev V, Kalev P . The deubiquitylase USP33 discriminates between RALB functions in autophagy and innate immune response. Nat Cell Biol. 2013; 15(10):1220-30. DOI: 10.1038/ncb2847. View