Nucleocapsid Protein of SARS-CoV-2 Upregulates RANTES Expression in A172 Glioblastoma Cells

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2025 Mar 13

PMID 40076291

Authors

Bakhytgul Gadilgereyeva

Zhanar Kunushpayeva

Mira Abdrakhmanova

Aizere Khassenova

Nail Minigulov

Timo Burster

Olena Filchakova

Affiliations

Soon will be listed here.

Abstract

SARS-CoV-2, the pathogenic virus that induces COVID-19 disease, contains four structural proteins in its virion. The nucleocapsid (N) protein is one of the four structural proteins that play a crucial role in the assembly of viral RNA into ribonucleoprotein. In addition, the N protein contributes to viral pathogenesis. One of the functions attributed to the N protein is the triggering of cytokine release by lung epithelial cells, macrophages, and monocytes. This study addresses the cellular effects of the N protein of SARS-CoV-2 on cells of glial origin. We report the upregulation of the RANTES chemokine in A172 glioblastoma cells at both the mRNA and protein levels in response to exposure to SARS-CoV-2 nucleocapsid protein. The N protein did not have an effect on cell viability and cell migration.

References

Chen C, Liao S, Kuo M, Wang Y . Astrocytic alteration induced by Japanese encephalitis virus infection. Neuroreport. 2000; 11(9):1933-7. DOI: 10.1097/00001756-200006260-00025. View

Montazersaheb S, Hosseiniyan Khatibi S, Hejazi M, Tarhriz V, Farjami A, Ghasemian Sorbeni F . COVID-19 infection: an overview on cytokine storm and related interventions. Virol J. 2022; 19(1):92. PMC: 9134144. DOI: 10.1186/s12985-022-01814-1. View

Naqvi A, Fatima K, Mohammad T, Fatima U, Singh I, Singh A . Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020; 1866(10):165878. PMC: 7293463. DOI: 10.1016/j.bbadis.2020.165878. View

Meinhardt J, Radke J, Dittmayer C, Franz J, Thomas C, Mothes R . Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. 2020; 24(2):168-175. DOI: 10.1038/s41593-020-00758-5. View

Balnis J, Adam A, Chopra A, Chieng H, Drake L, Martino N . Unique inflammatory profile is associated with higher SARS-CoV-2 acute respiratory distress syndrome (ARDS) mortality. Am J Physiol Regul Integr Comp Physiol. 2021; 320(3):R250-R257. PMC: 7938634. DOI: 10.1152/ajpregu.00324.2020. View

Kaphle P, Li Y, Yao L . The mechanical and pharmacological regulation of glioblastoma cell migration in 3D matrices. J Cell Physiol. 2018; 234(4):3948-3960. PMC: 8006216. DOI: 10.1002/jcp.27209. View

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y . Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223):497-506. PMC: 7159299. DOI: 10.1016/S0140-6736(20)30183-5. View

Deshmane S, Kremlev S, Amini S, Sawaya B . Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res. 2009; 29(6):313-26. PMC: 2755091. DOI: 10.1089/jir.2008.0027. View

Coomes E, Haghbayan H . Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med Virol. 2020; 30(6):1-9. PMC: 7460877. DOI: 10.1002/rmv.2141. View

10.

Palesch D, Wagner J, Meid A, Molenda N, Sienczyk M, Burkhardt J . Cathepsin G-mediated proteolytic degradation of MHC class I molecules to facilitate immune detection of human glioblastoma cells. Cancer Immunol Immunother. 2016; 65(3):283-91. PMC: 11028727. DOI: 10.1007/s00262-016-1798-5. View

11.

Mao L, Jin H, Wang M, Hu Y, Chen S, He Q . Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020; 77(6):683-690. PMC: 7149362. DOI: 10.1001/jamaneurol.2020.1127. View

12.

Tsukahara T, Brann D, Datta S . Mechanisms of SARS-CoV-2-associated anosmia. Physiol Rev. 2023; 103(4):2759-2766. PMC: 10625840. DOI: 10.1152/physrev.00012.2023. View

13.

Crawford A, Angelosanto J, Nadwodny K, Blackburn S, Wherry E . A role for the chemokine RANTES in regulating CD8 T cell responses during chronic viral infection. PLoS Pathog. 2011; 7(7):e1002098. PMC: 3141034. DOI: 10.1371/journal.ppat.1002098. View

14.

Appay V, Rowland-Jones S . RANTES: a versatile and controversial chemokine. Trends Immunol. 2001; 22(2):83-7. DOI: 10.1016/s1471-4906(00)01812-3. View

15.

Elbadawy H, Khattab A, El-Agamy D, Eltahir H, Alhaddad A, Aljohani F . IL-6 at the center of cytokine storm: Circulating inflammation mediators as biomarkers in hospitalized COVID-19 patients. J Clin Lab Anal. 2023; 37(7):e24881. PMC: 10220295. DOI: 10.1002/jcla.24881. View

16.

Patterson B, Seethamraju H, Dhody K, Corley M, Kazempour K, Lalezari J . CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14. Int J Infect Dis. 2020; 103:25-32. PMC: 7654230. DOI: 10.1016/j.ijid.2020.10.101. View

17.

Villalba M, Valdes Ramirez O, Mune Jimenez M, Arencibia Garcia A, Martinez Alfonso J, Gonzalez Baez G . Interferon gamma, TGF-β1 and RANTES expression in upper airway samples from SARS-CoV-2 infected patients. Clin Immunol. 2020; 220:108576. PMC: 7455570. DOI: 10.1016/j.clim.2020.108576. View

18.

Suarez-Arnedo A, Torres Figueroa F, Clavijo C, Arbelaez P, Cruz J, Munoz-Camargo C . An image J plugin for the high throughput image analysis of in vitro scratch wound healing assays. PLoS One. 2020; 15(7):e0232565. PMC: 7386569. DOI: 10.1371/journal.pone.0232565. View

19.

Zhang B, Tian J, Zhang Q, Xie Y, Wang K, Qiu S . Comparing the Nucleocapsid Proteins of Human Coronaviruses: Structure, Immunoregulation, Vaccine, and Targeted Drug. Front Mol Biosci. 2022; 9:761173. PMC: 9099148. DOI: 10.3389/fmolb.2022.761173. View

20.

Pan P, Ge W, Lei Z, Luo W, Liu Y, Guan Z . SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication. Signal Transduct Target Ther. 2023; 8(1):194. PMC: 10169150. DOI: 10.1038/s41392-023-01459-8. View