Transcriptional Landscape of Human Neuroblastoma Cells in Response to SARS-CoV-2

Overview

Journal BMC Neurosci

Publisher Biomed Central

Specialty Neurology

Date 2022 Jul 6

PMID 35794518

Authors

Rui-Cheng Yang

Kun Huang

Hui-Peng Zhang

Liang Li

Chen Tan

Huan-Chun Chen

Mei-Lin Jin

Xiang-Ru Wang

Affiliations

Soon will be listed here.

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious, and the neurological symptoms of SARS-CoV-2 infection have already been reported. However, the mechanisms underlying the effect of SARS-CoV-2 infection on patients with central nervous system injuries remain unclear.

Methods: The high-throughput RNA sequencing was applied to analyze the transcriptomic changes in SK-N-SH cells after SARS-CoV-2 infection. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to identify the functions of differentially expressed genes and related pathways.

Results: A total of 820 mRNAs were significantly altered, including 671 upregulated and 149 downregulated mRNAs (showing an increase of ≥ 2-fold or decrease to ≤ 0.5-fold, respectively; p ≤ 0.05). Moreover, we verified the significant induction of cytokines, chemokines, and their receptors, as well as the activation of NF-κB, p38, and Akt signaling pathways, in SK-N-SH by SARS-CoV-2.

Conclusions: To our knowledge, this is the first time the transcriptional profiles of the host mRNAs involved in SARS-CoV-2 infection of SK-N-SH cells have been reported. These findings provide novel insight into the pathogenic mechanism of SARS-CoV-2 and might constitute a new approach for future prevention and treatment of SARS-CoV-2-induced central nervous system infection.

Citing Articles

Viral Entry Inhibitors Protect against SARS-CoV-2-Induced Neurite Shortening in Differentiated SH-SY5Y Cells.

Mignolet M, Gilloteaux J, Halloin N, Gueibe M, Willemart K, De Swert K Viruses. 2023; 15(10).

PMID: 37896797 PMC: 10611151. DOI: 10.3390/v15102020.

Emerging role of non-coding RNAs in neuroinflammation mediated by microglia and astrocytes.

Yang R, Yang B, Liu W, Tan C, Chen H, Wang X J Neuroinflammation. 2023; 20(1):173.

PMID: 37481642 PMC: 10363317. DOI: 10.1186/s12974-023-02856-0.

Blood-Brain Barrier Integrity Damage in Bacterial Meningitis: The Underlying Link, Mechanisms, and Therapeutic Targets.

Yang R, Wang J, Wang F, Zhang H, Tan C, Chen H Int J Mol Sci. 2023; 24(3).

PMID: 36769171 PMC: 9918147. DOI: 10.3390/ijms24032852.

References

Huang K, Zhang Y, Hui X, Zhao Y, Gong W, Wang T . Q493K and Q498H substitutions in Spike promote adaptation of SARS-CoV-2 in mice. EBioMedicine. 2021; 67:103381. PMC: 8118724. DOI: 10.1016/j.ebiom.2021.103381. View

Shi Q, Wang X, Ju Z, Liu B, Lei C, Wang H . Technological and Safety Characterization of Isolates From Traditional Ethnic Dry-Cured Ham of Nuodeng, Southwest China. Front Microbiol. 2021; 12:761019. PMC: 8634685. DOI: 10.3389/fmicb.2021.761019. View

Desforges M, Le Coupanec A, Dubeau P, Bourgouin A, Lajoie L, Dube M . Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?. Viruses. 2019; 12(1). PMC: 7020001. DOI: 10.3390/v12010014. View

Yang R, Liu W, Miao L, Yang X, Fu J, Dou B . Induction of VEGFA and Snail-1 by meningitic Escherichia coli mediates disruption of the blood-brain barrier. Oncotarget. 2016; 7(39):63839-63855. PMC: 5325408. DOI: 10.18632/oncotarget.11696. View

Gu J, Gong E, Zhang B, Zheng J, Gao Z, Zhong Y . Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005; 202(3):415-24. PMC: 2213088. DOI: 10.1084/jem.20050828. View

Israelov H, Ravid O, Atrakchi D, Rand D, Elhaik S, Bresler Y . Caspase-1 has a critical role in blood-brain barrier injury and its inhibition contributes to multifaceted repair. J Neuroinflammation. 2020; 17(1):267. PMC: 7488082. DOI: 10.1186/s12974-020-01927-w. View

Wu D, Yang X . TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect. 2020; 53(3):368-370. PMC: 7156211. DOI: 10.1016/j.jmii.2020.03.005. View

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

Michael B, Bricio-Moreno L, Sorensen E, Miyabe Y, Lian J, Solomon T . Astrocyte- and Neuron-Derived CXCL1 Drives Neutrophil Transmigration and Blood-Brain Barrier Permeability in Viral Encephalitis. Cell Rep. 2020; 32(11):108150. PMC: 7548103. DOI: 10.1016/j.celrep.2020.108150. View

10.

Stamatovic S, Keep R, Kunkel S, Andjelkovic A . Potential role of MCP-1 in endothelial cell tight junction 'opening': signaling via Rho and Rho kinase. J Cell Sci. 2003; 116(Pt 22):4615-28. DOI: 10.1242/jcs.00755. View

11.

Li Y, Bai W, Hashikawa T . The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020; 92(6):552-555. PMC: 7228394. DOI: 10.1002/jmv.25728. View

12.

Puelles V, Lutgehetmann M, Lindenmeyer M, Sperhake J, Wong M, Allweiss L . Multiorgan and Renal Tropism of SARS-CoV-2. N Engl J Med. 2020; 383(6):590-592. PMC: 7240771. DOI: 10.1056/NEJMc2011400. View

13.

Yang Y, Shen C, Li J, Yuan J, Wei J, Huang F . Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. J Allergy Clin Immunol. 2020; 146(1):119-127.e4. PMC: 7189843. DOI: 10.1016/j.jaci.2020.04.027. View

14.

Das G, Mukherjee N, Ghosh S . Neurological Insights of COVID-19 Pandemic. ACS Chem Neurosci. 2020; 11(9):1206-1209. DOI: 10.1021/acschemneuro.0c00201. View

15.

Zang R, Gomez Castro M, McCune B, Zeng Q, Rothlauf P, Sonnek N . TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Sci Immunol. 2020; 5(47). PMC: 7285829. DOI: 10.1126/sciimmunol.abc3582. View

16.

Guilmot A, Slootjes S, Sellimi A, Bronchain M, Hanseeuw B, Belkhir L . Immune-mediated neurological syndromes in SARS-CoV-2-infected patients. J Neurol. 2020; 268(3):751-757. PMC: 7391231. DOI: 10.1007/s00415-020-10108-x. View

17.

Zhou Z, Kang H, Li S, Zhao X . Understanding the neurotropic characteristics of SARS-CoV-2: from neurological manifestations of COVID-19 to potential neurotropic mechanisms. J Neurol. 2020; 267(8):2179-2184. PMC: 7249973. DOI: 10.1007/s00415-020-09929-7. View

18.

Song E, Zhang C, Israelow B, Lu-Culligan A, Prado A, Skriabine S . Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med. 2021; 218(3). PMC: 7808299. DOI: 10.1084/jem.20202135. View

19.

Yang R, Huang F, Fu J, Dou B, Xu B, Miao L . Differential transcription profiles of long non-coding RNAs in primary human brain microvascular endothelial cells in response to meningitic Escherichia coli. Sci Rep. 2016; 6:38903. PMC: 5153642. DOI: 10.1038/srep38903. View

20.

Yang R, Qu X, Xiao S, Li L, Xu B, Fu J . Meningitic Escherichia coli-induced upregulation of PDGF-B and ICAM-1 aggravates blood-brain barrier disruption and neuroinflammatory response. J Neuroinflammation. 2019; 16(1):101. PMC: 6521501. DOI: 10.1186/s12974-019-1497-1. View