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dc.contributor.authorKulkarni, Amit
dc.contributor.authorFerreira, Tiago
dc.contributor.authorBretscher, Clemens
dc.contributor.authorGrewenig, Annabel
dc.contributor.authorEl-Andaloussi, Nazim
dc.contributor.authorBonifati, Serena
dc.contributor.authorMarttila, Tiina
dc.contributor.authorPalissot, Valèrie
dc.contributor.authorHossain, Jubayer A.
dc.contributor.authorAzuaje, Francisco
dc.contributor.authorMiletic, Hrvoje
dc.contributor.authorYstaas, Lars Andreas Rømo
dc.contributor.authorGolebiewska, Anna
dc.contributor.authorNiclou, Simone Pierrette
dc.contributor.authorRoeth, Ralf
dc.contributor.authorNiesler, Beate
dc.contributor.authorWeiss, Amélie
dc.contributor.authorBrino, Laurent
dc.contributor.authorMarchini, Antonio
dc.description.abstractH-1 parvovirus (H-1PV) is a promising anticancer therapy. However, in-depth understanding of its life cycle, including the host cell factors needed for infectivity and oncolysis, is lacking. This understanding may guide the rational design of combination strategies, aid development of more effective viruses, and help identify biomarkers of susceptibility to H-1PV treatment. To identify the host cell factors involved, we carry out siRNA library screening using a druggable genome library. We identify one crucial modulator of H-1PV infection: laminin γ1 (LAMC1). Using loss- and gain-of-function studies, competition experiments, and ELISA, we validate LAMC1 and laminin family members as being essential to H-1PV cell attachment and entry. H-1PV binding to laminins is dependent on their sialic acid moieties and is inhibited by heparin. We show that laminins are differentially expressed in various tumour entities, including glioblastoma. We confirm the expression pattern of laminin γ1 in glioblastoma biopsies by immunohistochemistry. We also provide evidence of a direct correlation between LAMC1 expression levels and H-1PV oncolytic activity in 59 cancer cell lines and in 3D organotypic spheroid cultures with different sensitivities to H-1PV infection. These results support the idea that tumours with elevated levels of γ1 containing laminins are more susceptible to H-1PV-based therapies.en_US
dc.publisherNature Researchen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleOncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entryen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2021 the authorsen_US
dc.source.journalNature Communicationsen_US
dc.identifier.citationNature Communications. 2021, 12, 3834.en_US

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