Zikavirus <i>pr</i>ME Envelope Pseudotyped Human Immunodeficiency Virus Type-1 as a Novel Tool for Glioblastoma-Directed Virotherapy
Glioblastoma multiforme is the most lethal type of brain tumor that is not yet curable owing to its frequent resurgence after surgery. Resistance is mainly caused by the presence of a subpopulation of tumor cells, the glioma stem cells (GSCs), which are highly resistant to radiation and chemotherapy...
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MDPI AG
2020-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/4/1000 |
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| author | Maibritt Kretschmer Patrycja Kadlubowska Daniel Hoffmann Birco Schwalbe Heidi Auerswald Michael Schreiber |
| author_facet | Maibritt Kretschmer Patrycja Kadlubowska Daniel Hoffmann Birco Schwalbe Heidi Auerswald Michael Schreiber |
| author_sort | Maibritt Kretschmer |
| collection | DOAJ |
| description | Glioblastoma multiforme is the most lethal type of brain tumor that is not yet curable owing to its frequent resurgence after surgery. Resistance is mainly caused by the presence of a subpopulation of tumor cells, the glioma stem cells (GSCs), which are highly resistant to radiation and chemotherapy. In 2015, Zikavirus (ZIKV)-induced microcephaly emerged in newborns, indicating that ZIKV has a specific neurotropism. Accordingly, an oncolytic tropism for infecting GSCs was demonstrated in a murine tumor model. Like other flaviviruses, ZIKV is enveloped by two proteins, <i>pr</i>M and E. The pME expression plasmid along with the HIV-1 vector pNL Luc AM generated <i>pr</i>ME pseudotyped viral particles. Four different <i>pr</i>ME envelopes, Z1 to Z4, were cloned, and the corresponding pseudotypes, Z1- to Z4-HIV<i>luc</i>, produced by this two-plasmid system, were tested for entry efficiency using Vero-B4 cells. The most efficient pseudotype, Z1-HIV<i>luc</i>, also infected glioma-derived cell lines U87 and 86HG39. The pseudotype system was then extended by using a three-plasmid system including pME-Z1, the HIV-1 packaging plasmid psPAX2, and the lentiviral vector pLenti-luciferase-P2A-Neo. The corresponding pseudotype, designated Z1-LENTI<i>luc</i>, also infected U87 and 86HG39 cells. Altogether, a pseudotyped virus especially targeting glioma-derived cells might be a promising candidate for a prospective glioblastoma-directed virotherapy. |
| first_indexed | 2024-03-10T20:22:52Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:22:52Z |
| publishDate | 2020-04-01 |
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| series | Cancers |
| spelling | doaj.art-0ecb5a0d915847caa52898676d1d441e2023-11-19T22:02:07ZengMDPI AGCancers2072-66942020-04-01124100010.3390/cancers12041000Zikavirus <i>pr</i>ME Envelope Pseudotyped Human Immunodeficiency Virus Type-1 as a Novel Tool for Glioblastoma-Directed VirotherapyMaibritt Kretschmer0Patrycja Kadlubowska1Daniel Hoffmann2Birco Schwalbe3Heidi Auerswald4Michael Schreiber5Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, D-20359 Hamburg, GermanyDepartment of Virology, Bernhard-Nocht Institute for Tropical Medicine, D-20359 Hamburg, GermanyDepartment of Virology, Bernhard-Nocht Institute for Tropical Medicine, D-20359 Hamburg, GermanyDepartment of Neurosurgery, Asklepios Klinik Nord—Heidberg, Asklepios Kliniken Hamburg GmbH, D-22417 Hamburg, GermanyDepartment of Virology, Bernhard-Nocht Institute for Tropical Medicine, D-20359 Hamburg, GermanyDepartment of Virology, Bernhard-Nocht Institute for Tropical Medicine, D-20359 Hamburg, GermanyGlioblastoma multiforme is the most lethal type of brain tumor that is not yet curable owing to its frequent resurgence after surgery. Resistance is mainly caused by the presence of a subpopulation of tumor cells, the glioma stem cells (GSCs), which are highly resistant to radiation and chemotherapy. In 2015, Zikavirus (ZIKV)-induced microcephaly emerged in newborns, indicating that ZIKV has a specific neurotropism. Accordingly, an oncolytic tropism for infecting GSCs was demonstrated in a murine tumor model. Like other flaviviruses, ZIKV is enveloped by two proteins, <i>pr</i>M and E. The pME expression plasmid along with the HIV-1 vector pNL Luc AM generated <i>pr</i>ME pseudotyped viral particles. Four different <i>pr</i>ME envelopes, Z1 to Z4, were cloned, and the corresponding pseudotypes, Z1- to Z4-HIV<i>luc</i>, produced by this two-plasmid system, were tested for entry efficiency using Vero-B4 cells. The most efficient pseudotype, Z1-HIV<i>luc</i>, also infected glioma-derived cell lines U87 and 86HG39. The pseudotype system was then extended by using a three-plasmid system including pME-Z1, the HIV-1 packaging plasmid psPAX2, and the lentiviral vector pLenti-luciferase-P2A-Neo. The corresponding pseudotype, designated Z1-LENTI<i>luc</i>, also infected U87 and 86HG39 cells. Altogether, a pseudotyped virus especially targeting glioma-derived cells might be a promising candidate for a prospective glioblastoma-directed virotherapy.https://www.mdpi.com/2072-6694/12/4/1000oncolytic viruseszika virusglioma stem cellsHIV-1pseudotyped virusneurotropism |
| spellingShingle | Maibritt Kretschmer Patrycja Kadlubowska Daniel Hoffmann Birco Schwalbe Heidi Auerswald Michael Schreiber Zikavirus <i>pr</i>ME Envelope Pseudotyped Human Immunodeficiency Virus Type-1 as a Novel Tool for Glioblastoma-Directed Virotherapy Cancers oncolytic viruses zika virus glioma stem cells HIV-1 pseudotyped virus neurotropism |
| title | Zikavirus <i>pr</i>ME Envelope Pseudotyped Human Immunodeficiency Virus Type-1 as a Novel Tool for Glioblastoma-Directed Virotherapy |
| title_full | Zikavirus <i>pr</i>ME Envelope Pseudotyped Human Immunodeficiency Virus Type-1 as a Novel Tool for Glioblastoma-Directed Virotherapy |
| title_fullStr | Zikavirus <i>pr</i>ME Envelope Pseudotyped Human Immunodeficiency Virus Type-1 as a Novel Tool for Glioblastoma-Directed Virotherapy |
| title_full_unstemmed | Zikavirus <i>pr</i>ME Envelope Pseudotyped Human Immunodeficiency Virus Type-1 as a Novel Tool for Glioblastoma-Directed Virotherapy |
| title_short | Zikavirus <i>pr</i>ME Envelope Pseudotyped Human Immunodeficiency Virus Type-1 as a Novel Tool for Glioblastoma-Directed Virotherapy |
| title_sort | zikavirus i pr i me envelope pseudotyped human immunodeficiency virus type 1 as a novel tool for glioblastoma directed virotherapy |
| topic | oncolytic viruses zika virus glioma stem cells HIV-1 pseudotyped virus neurotropism |
| url | https://www.mdpi.com/2072-6694/12/4/1000 |
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