Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry.

Autor: Kulkarni A; Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Center, Heidelberg, Germany.; Laboratory of Oncolytic Virus Immuno-Therapeutics, Luxembourg Institute of Health, Luxembourg, Luxembourg., Ferreira T; Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Center, Heidelberg, Germany., Bretscher C; Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Center, Heidelberg, Germany., Grewenig A; Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Center, Heidelberg, Germany., El-Andaloussi N; Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Center, Heidelberg, Germany.; Lonza Cologne GmbH, Köln, Germany., Bonifati S; Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Center, Heidelberg, Germany.; Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA., Marttila T; Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Center, Heidelberg, Germany.; Laboratory of Oncolytic Virus Immuno-Therapeutics, Luxembourg Institute of Health, Luxembourg, Luxembourg., Palissot V; Laboratory of Oncolytic Virus Immuno-Therapeutics, Luxembourg Institute of Health, Luxembourg, Luxembourg., Hossain JA; Laboratory of Oncolytic Virus Immuno-Therapeutics, Luxembourg Institute of Health, Luxembourg, Luxembourg.; Department of Biomedicine, University of Bergen, Bergen, Norway.; Department of Pathology, Haukeland University Hospital, Bergen, Norway., Azuaje F; Quantitative Biology Unit, Luxembourg Institute of Health, Luxembourg, Luxembourg.; Genomics England, London, United Kingdom., Miletic H; Department of Biomedicine, University of Bergen, Bergen, Norway.; Department of Pathology, Haukeland University Hospital, Bergen, Norway., Ystaas LAR; Department of Biomedicine, University of Bergen, Bergen, Norway., Golebiewska A; NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg., Niclou SP; NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg., Roeth R; nCounter Core Facility, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.; Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany., Niesler B; nCounter Core Facility, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.; Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, Germany., Weiss A; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France., Brino L; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France., Marchini A; Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Center, Heidelberg, Germany. antonio.marchini@lih.lu.; Laboratory of Oncolytic Virus Immuno-Therapeutics, Luxembourg Institute of Health, Luxembourg, Luxembourg. antonio.marchini@lih.lu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jun 22; Vol. 12 (1), pp. 3834. Date of Electronic Publication: 2021 Jun 22.
DOI: 10.1038/s41467-021-24034-7
Abstrakt: H-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.
Databáze: MEDLINE
Externí odkaz: