Multiscale Network Analysis Identifies Potential Receptors for SARS-CoV-2 and Reveals Their Tissue-specific and Age-dependent Expression

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2023 Mar 23

PMID 36951513

Authors

Christian V Forst

Lu Zeng

Qian Wang

Xianxiao Zhou

Sezen Vatansever

Peng Xu

Won-Min Song

Zhidong Tu

Bin Zhang

Affiliations

Soon will be listed here.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has affected tens of millions of individuals and caused hundreds of thousands of deaths worldwide. Here, we present a comprehensive, multiscale network analysis of the transcriptional response to the virus. In particular, we focused on key regulators, cell receptors, and host processes that were hijacked by the virus for its advantage. ACE2-controlled processes involved CD300e (a TYROBP receptor) as a key regulator and the activation of IL-2 pro-inflammatory cytokine signaling. We further investigated the age dependency of such receptors in different tissues. In summary, this study provides novel insights into the gene regulatory organization during the SARS-CoV-2 infection and the tissue-specific, age-dependent expression of the cell receptors involved in COVID-19.

Citing Articles

Unsupervised multi-scale clustering of single-cell transcriptomes to identify hierarchical structures of cell subtypes.

Song W, Ming C, Forst C, Zhang B Res Sq. 2025; .

PMID: 39764102 PMC: 11703337. DOI: 10.21203/rs.3.rs-5671748/v1.

References

Singh M, Bansal V, Feschotte C . A Single-Cell RNA Expression Map of Human Coronavirus Entry Factors. Cell Rep. 2020; 32(12):108175. PMC: 7470764. DOI: 10.1016/j.celrep.2020.108175. View

Zhu R, Yan T, Feng Y, Liu Y, Cao H, Peng G . Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms. Cell Res. 2021; 31(12):1244-1262. PMC: 8546390. DOI: 10.1038/s41422-021-00573-y. View

Zenarruzabeitia O, Vitalle J, Garcia-Obregon S, Astigarraga I, Eguizabal C, Santos S . The expression and function of human CD300 receptors on blood circulating mononuclear cells are distinct in neonates and adults. Sci Rep. 2016; 6:32693. PMC: 5011699. DOI: 10.1038/srep32693. View

Liu Y, Chen S, Li Z, Morrison A, Boerwinkle E, Lin X . ACAT: A Fast and Powerful p Value Combination Method for Rare-Variant Analysis in Sequencing Studies. Am J Hum Genet. 2019; 104(3):410-421. PMC: 6407498. DOI: 10.1016/j.ajhg.2019.01.002. View

Zeng L, Yang J, Peng S, Zhu J, Zhang B, Suh Y . Transcriptome analysis reveals the difference between "healthy" and "common" aging and their connection with age-related diseases. Aging Cell. 2020; 19(3):e13121. PMC: 7059150. DOI: 10.1111/acel.13121. View

Muus C, Luecken M, Eraslan G, Sikkema L, Waghray A, Heimberg G . Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat Med. 2021; 27(3):546-559. PMC: 9469728. DOI: 10.1038/s41591-020-01227-z. View

Smith T, Rohaim M, Munir M . Mapping molecular gene signatures mediated by SARS-COV-2 and large-scale and genome-wide transcriptomics comparative analysis among respiratory viruses of medical importance. Mol Cell Probes. 2022; 64:101820. PMC: 9054707. DOI: 10.1016/j.mcp.2022.101820. View

Vanderheiden A, Klein R . Neuroinflammation and COVID-19. Curr Opin Neurobiol. 2022; 76:102608. PMC: 9239981. DOI: 10.1016/j.conb.2022.102608. View

Wang I, Zhang B, Yang X, Zhu J, Stepaniants S, Zhang C . Systems analysis of eleven rodent disease models reveals an inflammatome signature and key drivers. Mol Syst Biol. 2012; 8:594. PMC: 3421440. DOI: 10.1038/msb.2012.24. View

10.

Cantuti-Castelvetri L, Ojha R, Pedro L, Djannatian M, Franz J, Kuivanen S . Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science. 2020; 370(6518):856-860. PMC: 7857391. DOI: 10.1126/science.abd2985. View

11.

Zhou Z, Xue Q, Wan Y, Yang Y, Wang J, Hung T . Lysosome-associated membrane glycoprotein 3 is involved in influenza A virus replication in human lung epithelial (A549) cells. Virol J. 2011; 8:384. PMC: 3162545. DOI: 10.1186/1743-422X-8-384. View

12.

Proudfoot A . Chemokine receptors: multifaceted therapeutic targets. Nat Rev Immunol. 2002; 2(2):106-15. PMC: 7097668. DOI: 10.1038/nri722. View

13.

Cormier E, Tsamis F, Kajumo F, Durso R, Gardner J, Dragic T . CD81 is an entry coreceptor for hepatitis C virus. Proc Natl Acad Sci U S A. 2004; 101(19):7270-4. PMC: 409908. DOI: 10.1073/pnas.0402253101. View

14.

Wang M, Zhao Y, Zhang B . Efficient Test and Visualization of Multi-Set Intersections. Sci Rep. 2015; 5:16923. PMC: 4658477. DOI: 10.1038/srep16923. View

15.

Bausch-Fluck D, Hofmann A, Bock T, Frei A, Cerciello F, Jacobs A . A mass spectrometric-derived cell surface protein atlas. PLoS One. 2015; 10(3):e0121314. PMC: 4404347. DOI: 10.1371/journal.pone.0121314. View

16.

Zhao Y, Forst C, Sayegh C, Wang I, Yang X, Zhang B . Molecular and genetic inflammation networks in major human diseases. Mol Biosyst. 2016; 12(8):2318-41. PMC: 4955784. DOI: 10.1039/c6mb00240d. View

17.

Bausch-Fluck D, Goldmann U, Muller S, van Oostrum M, Muller M, Schubert O . The in silico human surfaceome. Proc Natl Acad Sci U S A. 2018; 115(46):E10988-E10997. PMC: 6243280. DOI: 10.1073/pnas.1808790115. View

18.

Brckalo T, Calzetti F, Perez-Cabezas B, Borras F, Cassatella M, Lopez-Botet M . Functional analysis of the CD300e receptor in human monocytes and myeloid dendritic cells. Eur J Immunol. 2009; 40(3):722-32. DOI: 10.1002/eji.200939468. View

19.

Lasswitz L, Zapatero-Belinchon F, Moeller R, Hulskotter K, Laurent T, Carlson L . The Tetraspanin CD81 Is a Host Factor for Chikungunya Virus Replication. mBio. 2022; 13(3):e0073122. PMC: 9239085. DOI: 10.1128/mbio.00731-22. View

20.

Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J . Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med. 2020; 26(6):842-844. DOI: 10.1038/s41591-020-0901-9. View