Oncolytic H-1 Parvovirus Hijacks Galectin-1 to Enter Cancer Cells

Tiago Ferreira, Amit Kulkarni, Clemens Bretscher, Petr V. Nazarov, Jubayer A. Hossain, Lars A.R. Ystaas, Hrvoje Miletic, Ralph Röth, Beate Niesler, Antonio Marchini*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Clinical studies in glioblastoma and pancreatic carcinoma patients strongly support the further development of H-1 protoparvovirus (H-1PV)-based anticancer therapies. The identification of cellular factors involved in the H-1PV life cycle may provide the knowledge to improve H-1PV anticancer potential. Recently, we showed that sialylated laminins mediate H-1PV attachment at the cell membrane. In this study, we revealed that H-1PV also interacts at the cell surface with galectin-1 and uses this glycoprotein to enter cancer cells. Indeed, knockdown/out of LGALS1, the gene encoding galectin-1, strongly decreases the ability of H-1PV to infect and kill cancer cells. This ability is rescued by the re-introduction of LGALS1 into cancer cells. Pre-treatment with lactose, which is able to bind to galectins and modulate their cellular functions, decreased H-1PV infectivity in a dose dependent manner. In silico analysis reveals that LGALS1 is overexpressed in various tumours including glioblastoma and pancreatic carcinoma. We show by immunohistochemistry analysis of 122 glioblastoma biopsies that galectin-1 protein levels vary between tumours, with levels in recurrent glioblastoma higher than those in primary tumours or normal tissues. We also find a direct correlation between LGALS1 transcript levels and H-1PV oncolytic activity in 53 cancer cell lines from different tumour origins. Strikingly, the addition of purified galectin-1 sensitises poorly susceptible GBM cell lines to H-1PV killing activity by rescuing cell entry. Together, these findings demonstrate that galectin-1 is a crucial determinant of the H-1PV life cycle.

Original languageEnglish
Article number1018
JournalViruses
Volume14
Issue number5
DOIs
Publication statusPublished - 11 May 2022

Keywords

  • galectin-1
  • laminin γ1
  • oncolytic virus immunotherapy
  • protoparvovirus H-1PV
  • virus cell entry
  • virus host interactions

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