Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus
Glioblastoma multiforme (GBM) accounts for almost half of all primary malignant brain tumors in adults and has a poor prognosis. Here we demonstrated the oncolytic potential of the L-16 vaccine strain of measles virus (MV) against primary human GBM cells and characterized the genetic patterns that d...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/14/11/2433 |
| _version_ | 1797466269703733248 |
|---|---|
| author | Yulia Ammour Olga Susova George Krasnov Eugenia Nikolaeva Vyacheslav Varachev Yulia Schetinina Marina Gavrilova Alexey Mitrofanov Anna Poletaeva Ali Bekyashev Evgeny Faizuloev Vitaly V. Zverev Oxana A. Svitich Tatiana V. Nasedkina |
| author_facet | Yulia Ammour Olga Susova George Krasnov Eugenia Nikolaeva Vyacheslav Varachev Yulia Schetinina Marina Gavrilova Alexey Mitrofanov Anna Poletaeva Ali Bekyashev Evgeny Faizuloev Vitaly V. Zverev Oxana A. Svitich Tatiana V. Nasedkina |
| author_sort | Yulia Ammour |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) accounts for almost half of all primary malignant brain tumors in adults and has a poor prognosis. Here we demonstrated the oncolytic potential of the L-16 vaccine strain of measles virus (MV) against primary human GBM cells and characterized the genetic patterns that determine the sensitivity of primary human GBM cells to oncolytic therapy. MV replicated in all GBM cells, and seven out of eight cell lines underwent complete or partial oncolysis. RNA-Seq analysis identified about 1200 differentially expressed genes (FDR < 0.05) with at least two-fold expression level change between MV-infected and uninfected cells. Among them, the most significant upregulation was observed for interferon response, apoptosis and cytokine signaling. One out of eight GBM cell lines was defective in type I interferon production and, thus, in the post-interferon response, other cells lacked expression of different cellular defense factors. Thus, none of the cell lines displayed induction of the total gene set necessary for effective inhibition of MV replication. In the resistant cells, we detected aberrant expression of metalloproteinase genes, particularly <i>MMP3</i>. Thus, such genes could be considered intriguing candidates for further study of factors responsible for cell sensitivity and resistance to L-16 MV infection. |
| first_indexed | 2024-03-09T18:34:31Z |
| format | Article |
| id | doaj.art-a503a91ea0db4e8d9b2b168b7b45b4f5 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T18:34:31Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a503a91ea0db4e8d9b2b168b7b45b4f52023-11-24T07:17:08ZengMDPI AGViruses1999-49152022-11-011411243310.3390/v14112433Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles VirusYulia Ammour0Olga Susova1George Krasnov2Eugenia Nikolaeva3Vyacheslav Varachev4Yulia Schetinina5Marina Gavrilova6Alexey Mitrofanov7Anna Poletaeva8Ali Bekyashev9Evgeny Faizuloev10Vitaly V. Zverev11Oxana A. Svitich12Tatiana V. Nasedkina13I.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, RussiaN.N. Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation, 115478 Moscow, RussiaEngelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 119991 Moscow, RussiaI.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, RussiaEngelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 119991 Moscow, RussiaI.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, RussiaI.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, RussiaN.N. Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation, 115478 Moscow, RussiaN.N. Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation, 115478 Moscow, RussiaN.N. Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation, 115478 Moscow, RussiaI.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, RussiaI.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, RussiaI.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, RussiaEngelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 119991 Moscow, RussiaGlioblastoma multiforme (GBM) accounts for almost half of all primary malignant brain tumors in adults and has a poor prognosis. Here we demonstrated the oncolytic potential of the L-16 vaccine strain of measles virus (MV) against primary human GBM cells and characterized the genetic patterns that determine the sensitivity of primary human GBM cells to oncolytic therapy. MV replicated in all GBM cells, and seven out of eight cell lines underwent complete or partial oncolysis. RNA-Seq analysis identified about 1200 differentially expressed genes (FDR < 0.05) with at least two-fold expression level change between MV-infected and uninfected cells. Among them, the most significant upregulation was observed for interferon response, apoptosis and cytokine signaling. One out of eight GBM cell lines was defective in type I interferon production and, thus, in the post-interferon response, other cells lacked expression of different cellular defense factors. Thus, none of the cell lines displayed induction of the total gene set necessary for effective inhibition of MV replication. In the resistant cells, we detected aberrant expression of metalloproteinase genes, particularly <i>MMP3</i>. Thus, such genes could be considered intriguing candidates for further study of factors responsible for cell sensitivity and resistance to L-16 MV infection.https://www.mdpi.com/1999-4915/14/11/2433oncolytic virusescancer immunotherapymeasles virusglioblastoma multiforme |
| spellingShingle | Yulia Ammour Olga Susova George Krasnov Eugenia Nikolaeva Vyacheslav Varachev Yulia Schetinina Marina Gavrilova Alexey Mitrofanov Anna Poletaeva Ali Bekyashev Evgeny Faizuloev Vitaly V. Zverev Oxana A. Svitich Tatiana V. Nasedkina Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus Viruses oncolytic viruses cancer immunotherapy measles virus glioblastoma multiforme |
| title | Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus |
| title_full | Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus |
| title_fullStr | Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus |
| title_full_unstemmed | Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus |
| title_short | Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus |
| title_sort | transcriptome analysis of human glioblastoma cells susceptible to infection with the leningrad 16 vaccine strain of measles virus |
| topic | oncolytic viruses cancer immunotherapy measles virus glioblastoma multiforme |
| url | https://www.mdpi.com/1999-4915/14/11/2433 |
| work_keys_str_mv | AT yuliaammour transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT olgasusova transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT georgekrasnov transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT eugenianikolaeva transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT vyacheslavvarachev transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT yuliaschetinina transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT marinagavrilova transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT alexeymitrofanov transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT annapoletaeva transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT alibekyashev transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT evgenyfaizuloev transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT vitalyvzverev transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT oxanaasvitich transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus AT tatianavnasedkina transcriptomeanalysisofhumanglioblastomacellssusceptibletoinfectionwiththeleningrad16vaccinestrainofmeaslesvirus |