Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A.

Mammalian Reovirus is a double-stranded RNA virus with a distinctive preference to replicate in and lyse transformed cells. On that account, Reovirus type 3 Dearing (T3D) is clinically evaluated as oncolytic agent. The therapeutic efficacy of this approach depends in part on the accessibility of the...

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Autores principales:	Diana J M van den Wollenberg, Iris J C Dautzenberg, Sanne K van den Hengel, Steve J Cramer, Raoul J de Groot, Rob C Hoeben
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f188a33e083a4395bb834fe1fedf0c5c
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spelling	oai:doaj.org-article:f188a33e083a4395bb834fe1fedf0c5c2021-11-18T08:11:16ZIsolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A.1932-620310.1371/journal.pone.0048064https://doaj.org/article/f188a33e083a4395bb834fe1fedf0c5c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23110175/?tool=EBIhttps://doaj.org/toc/1932-6203Mammalian Reovirus is a double-stranded RNA virus with a distinctive preference to replicate in and lyse transformed cells. On that account, Reovirus type 3 Dearing (T3D) is clinically evaluated as oncolytic agent. The therapeutic efficacy of this approach depends in part on the accessibility of the reovirus receptor Junction Adhesion Molecule-A (JAM-A) on the target cells. Here, we describe the isolation and characterization of reovirus T3D mutants that can infect human tumor cells independent of JAM-A. The JAM-A-independent (jin) mutants were isolated on human U118MG glioblastoma cells, which do not express JAM-A. All jin mutants harbour mutations in the S1 segments close to the region that encodes the sialic acid-binding pocket in the shaft of the spike protein. In addition, two of the jin mutants encode spike proteins with a Q336R substitution in their head domain. The jin mutants can productively infect a wide range of cell lines that resist wt reovirus T3D infection, including chicken LMH cells, hamster CHO cells, murine endothelioma cells, human U2OS and STA-ET2.1 cells, but not primary human fibroblasts. The jin-mutants rely on the presence of sialic-acid residues on the cell surface for productive infection, as is evident from wheat germ agglutinin (WGA) inhibition experiments, and from the jin-reovirus resistance of CHO-Lec2 cells, which have a deficiency of sialic-acids on their glycoproteins. The jin mutants may be useful as oncolytic agents for use in tumors in which JAM-A is absent or inaccessible.Diana J M van den WollenbergIris J C DautzenbergSanne K van den HengelSteve J CramerRaoul J de GrootRob C HoebenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e48064 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diana J M van den Wollenberg Iris J C Dautzenberg Sanne K van den Hengel Steve J Cramer Raoul J de Groot Rob C Hoeben Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A.
description	Mammalian Reovirus is a double-stranded RNA virus with a distinctive preference to replicate in and lyse transformed cells. On that account, Reovirus type 3 Dearing (T3D) is clinically evaluated as oncolytic agent. The therapeutic efficacy of this approach depends in part on the accessibility of the reovirus receptor Junction Adhesion Molecule-A (JAM-A) on the target cells. Here, we describe the isolation and characterization of reovirus T3D mutants that can infect human tumor cells independent of JAM-A. The JAM-A-independent (jin) mutants were isolated on human U118MG glioblastoma cells, which do not express JAM-A. All jin mutants harbour mutations in the S1 segments close to the region that encodes the sialic acid-binding pocket in the shaft of the spike protein. In addition, two of the jin mutants encode spike proteins with a Q336R substitution in their head domain. The jin mutants can productively infect a wide range of cell lines that resist wt reovirus T3D infection, including chicken LMH cells, hamster CHO cells, murine endothelioma cells, human U2OS and STA-ET2.1 cells, but not primary human fibroblasts. The jin-mutants rely on the presence of sialic-acid residues on the cell surface for productive infection, as is evident from wheat germ agglutinin (WGA) inhibition experiments, and from the jin-reovirus resistance of CHO-Lec2 cells, which have a deficiency of sialic-acids on their glycoproteins. The jin mutants may be useful as oncolytic agents for use in tumors in which JAM-A is absent or inaccessible.
format	article
author	Diana J M van den Wollenberg Iris J C Dautzenberg Sanne K van den Hengel Steve J Cramer Raoul J de Groot Rob C Hoeben
author_facet	Diana J M van den Wollenberg Iris J C Dautzenberg Sanne K van den Hengel Steve J Cramer Raoul J de Groot Rob C Hoeben
author_sort	Diana J M van den Wollenberg
title	Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A.
title_short	Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A.
title_full	Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A.
title_fullStr	Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A.
title_full_unstemmed	Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A.
title_sort	isolation of reovirus t3d mutants capable of infecting human tumor cells independent of junction adhesion molecule-a.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f188a33e083a4395bb834fe1fedf0c5c
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Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A.

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