TY  - JOUR
AU  - Ferreira, Tiago
AU  - Kulkarni, Amit
AU  - Bretscher, Clemens
AU  - Richter, Karsten
AU  - Ehrlich, Marcelo
AU  - Marchini, Antonio
TI  - Oncolytic H-1 Parvovirus Enters Cancer Cells through Clathrin-Mediated Endocytosis.
JO  - Viruses
VL  - 12
IS  - 10
SN  - 1999-4915
CY  - Basel
PB  - MDPI
M1  - DKFZ-2020-02277
SP  - 1199
PY  - 2020
N1  - #EA:F011#LA:F011# / #DKFZ-MOST-Ca184#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:33096814
DO  - DOI:10.3390/v12101199
UR  - https://inrepo02.dkfz.de/record/164137
ER  -