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Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry
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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219832/ https://www.ncbi.nlm.nih.gov/pubmed/34158478 http://dx.doi.org/10.1038/s41467-021-24034-7 |
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author | Kulkarni, Amit Ferreira, Tiago Bretscher, Clemens Grewenig, Annabel El-Andaloussi, Nazim Bonifati, Serena Marttila, Tiina Palissot, Valérie Hossain, Jubayer A. Azuaje, Francisco Miletic, Hrvoje Ystaas, Lars A. R. Golebiewska, Anna Niclou, Simone P. Roeth, Ralf Niesler, Beate Weiss, Amélie Brino, Laurent Marchini, Antonio |
author_facet | Kulkarni, Amit Ferreira, Tiago Bretscher, Clemens Grewenig, Annabel El-Andaloussi, Nazim Bonifati, Serena Marttila, Tiina Palissot, Valérie Hossain, Jubayer A. Azuaje, Francisco Miletic, Hrvoje Ystaas, Lars A. R. Golebiewska, Anna Niclou, Simone P. Roeth, Ralf Niesler, Beate Weiss, Amélie Brino, Laurent Marchini, Antonio |
author_sort | Kulkarni, Amit |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8219832 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82198322021-07-09 Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry Kulkarni, Amit Ferreira, Tiago Bretscher, Clemens Grewenig, Annabel El-Andaloussi, Nazim Bonifati, Serena Marttila, Tiina Palissot, Valérie Hossain, Jubayer A. Azuaje, Francisco Miletic, Hrvoje Ystaas, Lars A. R. Golebiewska, Anna Niclou, Simone P. Roeth, Ralf Niesler, Beate Weiss, Amélie Brino, Laurent Marchini, Antonio Nat Commun Article 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. Nature Publishing Group UK 2021-06-22 /pmc/articles/PMC8219832/ /pubmed/34158478 http://dx.doi.org/10.1038/s41467-021-24034-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Kulkarni, Amit Ferreira, Tiago Bretscher, Clemens Grewenig, Annabel El-Andaloussi, Nazim Bonifati, Serena Marttila, Tiina Palissot, Valérie Hossain, Jubayer A. Azuaje, Francisco Miletic, Hrvoje Ystaas, Lars A. R. Golebiewska, Anna Niclou, Simone P. Roeth, Ralf Niesler, Beate Weiss, Amélie Brino, Laurent Marchini, Antonio Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry |
title | Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry |
title_full | Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry |
title_fullStr | Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry |
title_full_unstemmed | Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry |
title_short | Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry |
title_sort | oncolytic h-1 parvovirus binds to sialic acid on laminins for cell attachment and entry |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219832/ https://www.ncbi.nlm.nih.gov/pubmed/34158478 http://dx.doi.org/10.1038/s41467-021-24034-7 |
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