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Article

Oncolytic H-1 Parvovirus Enters Cancer Cells through Clathrin-Mediated Endocytosis

1
Laboratory of Oncolytic Virus Immuno-Therapeutics, German Cancer Research Centre, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
2
Laboratory of Oncolytic Virus Immuno-Therapeutics, Luxembourg Institute of Health, 84 Val Fleuri, L-1526 Luxembourg, Luxembourg
3
Core Facility Electron Microscopy, German Cancer Research Centre, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
4
Laboratory of Signal Transduction and Membrane Biology, The Shumins School for Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Lux69978 Tel Aviv, Israel
*
Author to whom correspondence should be addressed.
Received: 8 October 2020 / Revised: 16 October 2020 / Accepted: 19 October 2020 / Published: 21 October 2020
(This article belongs to the Special Issue Advances in Parvovirus Research 2020)
H-1 protoparvovirus (H-1PV) is a self-propagating virus that is non-pathogenic in humans and has oncolytic and oncosuppressive activities. H-1PV is the first member of the Parvoviridae family to undergo clinical testing as an anticancer agent. Results from clinical trials in patients with glioblastoma or pancreatic carcinoma show that virus treatment is safe, well-tolerated and associated with first signs of efficacy. Characterisation of the H-1PV life cycle may help to improve its efficacy and clinical outcome. In this study, we investigated the entry route of H-1PV in cervical carcinoma HeLa and glioma NCH125 cell lines. Using electron and confocal microscopy, we detected H-1PV particles within clathrin-coated pits and vesicles, providing evidence that the virus uses clathrin-mediated endocytosis for cell entry. In agreement with these results, we found that blocking clathrin-mediated endocytosis using specific inhibitors or small interfering RNA-mediated knockdown of its key regulator, AP2M1, markedly reduced H-1PV entry. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. We also show that H-1PV entry is dependent on dynamin, while viral trafficking occurs from early to late endosomes, with acidic pH necessary for a productive infection. This is the first study that characterises the cell entry pathways of oncolytic H-1PV. View Full-Text
Keywords: oncolytic viruses; rodent protoparvovirus H-1PV; virus entry; clathrin-mediated endocytosis oncolytic viruses; rodent protoparvovirus H-1PV; virus entry; clathrin-mediated endocytosis
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MDPI and ACS Style

Ferreira, T.; Kulkarni, A.; Bretscher, C.; Richter, K.; Ehrlich, M.; Marchini, A. Oncolytic H-1 Parvovirus Enters Cancer Cells through Clathrin-Mediated Endocytosis. Viruses 2020, 12, 1199. https://0-doi-org.brum.beds.ac.uk/10.3390/v12101199

AMA Style

Ferreira T, Kulkarni A, Bretscher C, Richter K, Ehrlich M, Marchini A. Oncolytic H-1 Parvovirus Enters Cancer Cells through Clathrin-Mediated Endocytosis. Viruses. 2020; 12(10):1199. https://0-doi-org.brum.beds.ac.uk/10.3390/v12101199

Chicago/Turabian Style

Ferreira, Tiago, Amit Kulkarni, Clemens Bretscher, Karsten Richter, Marcelo Ehrlich, and Antonio Marchini. 2020. "Oncolytic H-1 Parvovirus Enters Cancer Cells through Clathrin-Mediated Endocytosis" Viruses 12, no. 10: 1199. https://0-doi-org.brum.beds.ac.uk/10.3390/v12101199

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