AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines

Recent reports have shown that Zika virus (ZIKV) has oncolytic potential against human glioblastoma (GBM); however, the mechanisms underlying its tropism and cell entry are not completely understood. The receptor tyrosine kinase AXL has been identified as an entry receptor for ZIKV in a cell-type-sp...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Samuel D. Zwernik, Beau H. Adams, Daniel A. Raymond, Catherine M. Warner, Amin B. Kassam, Richard A. Rovin, Parvez Akhtar
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	GBM Brain tumor AXL receptor Zika virus Oncolytic virus Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/18d95f4f8641431188e8a1028bee0efc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:18d95f4f8641431188e8a1028bee0efc
record_format	dspace
spelling	oai:doaj.org-article:18d95f4f8641431188e8a1028bee0efc2021-11-26T04:35:12ZAXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines2372-770510.1016/j.omto.2021.11.001https://doaj.org/article/18d95f4f8641431188e8a1028bee0efc2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2372770521001509https://doaj.org/toc/2372-7705Recent reports have shown that Zika virus (ZIKV) has oncolytic potential against human glioblastoma (GBM); however, the mechanisms underlying its tropism and cell entry are not completely understood. The receptor tyrosine kinase AXL has been identified as an entry receptor for ZIKV in a cell-type-specific manner. Interestingly, AXL is frequently overexpressed in GBM patients. Using commercially available GBM cell lines, we first show that cells expressing AXL are permissive for ZIKV infection, while cells that do not express AXL are not. Furthermore, inhibition of AXL kinase using R428 and antibody blockade of AXL receptor strongly attenuated virus entry in GBM cell lines. Additionally, CRISPR knockout of the AXL gene in GBM cell lines completely abolished ZIKV infection, significantly inhibited viral replication, and significantly reduced apoptosis compared with parental lines. Lastly, introduction of AXL receptor into non-expressing cell lines renders the cells susceptible to ZIKV infection. Together, these findings demonstrate that ZIKV entry into GBM cells in vitro is mediated by the AXL receptor and that following cell entry, productive infection is cytotoxic. Thus, ZIKV is a potential oncolytic virus for GBM.Samuel D. ZwernikBeau H. AdamsDaniel A. RaymondCatherine M. WarnerAmin B. KassamRichard A. RovinParvez AkhtarElsevierarticleGBMBrain tumorAXL receptorZika virusOncolytic virusNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Therapy: Oncolytics, Vol 23, Iss , Pp 447-457 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	GBM Brain tumor AXL receptor Zika virus Oncolytic virus Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	GBM Brain tumor AXL receptor Zika virus Oncolytic virus Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Samuel D. Zwernik Beau H. Adams Daniel A. Raymond Catherine M. Warner Amin B. Kassam Richard A. Rovin Parvez Akhtar AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
description	Recent reports have shown that Zika virus (ZIKV) has oncolytic potential against human glioblastoma (GBM); however, the mechanisms underlying its tropism and cell entry are not completely understood. The receptor tyrosine kinase AXL has been identified as an entry receptor for ZIKV in a cell-type-specific manner. Interestingly, AXL is frequently overexpressed in GBM patients. Using commercially available GBM cell lines, we first show that cells expressing AXL are permissive for ZIKV infection, while cells that do not express AXL are not. Furthermore, inhibition of AXL kinase using R428 and antibody blockade of AXL receptor strongly attenuated virus entry in GBM cell lines. Additionally, CRISPR knockout of the AXL gene in GBM cell lines completely abolished ZIKV infection, significantly inhibited viral replication, and significantly reduced apoptosis compared with parental lines. Lastly, introduction of AXL receptor into non-expressing cell lines renders the cells susceptible to ZIKV infection. Together, these findings demonstrate that ZIKV entry into GBM cells in vitro is mediated by the AXL receptor and that following cell entry, productive infection is cytotoxic. Thus, ZIKV is a potential oncolytic virus for GBM.
format	article
author	Samuel D. Zwernik Beau H. Adams Daniel A. Raymond Catherine M. Warner Amin B. Kassam Richard A. Rovin Parvez Akhtar
author_facet	Samuel D. Zwernik Beau H. Adams Daniel A. Raymond Catherine M. Warner Amin B. Kassam Richard A. Rovin Parvez Akhtar
author_sort	Samuel D. Zwernik
title	AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title_short	AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title_full	AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title_fullStr	AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title_full_unstemmed	AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines
title_sort	axl receptor is required for zika virus strain mr-766 infection in human glioblastoma cell lines
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/18d95f4f8641431188e8a1028bee0efc
work_keys_str_mv	AT samueldzwernik axlreceptorisrequiredforzikavirusstrainmr766infectioninhumanglioblastomacelllines AT beauhadams axlreceptorisrequiredforzikavirusstrainmr766infectioninhumanglioblastomacelllines AT danielaraymond axlreceptorisrequiredforzikavirusstrainmr766infectioninhumanglioblastomacelllines AT catherinemwarner axlreceptorisrequiredforzikavirusstrainmr766infectioninhumanglioblastomacelllines AT aminbkassam axlreceptorisrequiredforzikavirusstrainmr766infectioninhumanglioblastomacelllines AT richardarovin axlreceptorisrequiredforzikavirusstrainmr766infectioninhumanglioblastomacelllines AT parvezakhtar axlreceptorisrequiredforzikavirusstrainmr766infectioninhumanglioblastomacelllines
_version_	1718409825421885440

AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines

Ejemplares similares