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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...

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Autores principales: Ammour, Yulia, Susova, Olga, Krasnov, George, Nikolaeva, Eugenia, Varachev, Vyacheslav, Schetinina, Yulia, Gavrilova, Marina, Mitrofanov, Alexey, Poletaeva, Anna, Bekyashev, Ali, Faizuloev, Evgeny, Zverev, Vitaly V., Svitich, Oxana A., Nasedkina, Tatiana V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696624/
https://www.ncbi.nlm.nih.gov/pubmed/36366531
http://dx.doi.org/10.3390/v14112433
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author Ammour, Yulia
Susova, Olga
Krasnov, George
Nikolaeva, Eugenia
Varachev, Vyacheslav
Schetinina, Yulia
Gavrilova, Marina
Mitrofanov, Alexey
Poletaeva, Anna
Bekyashev, Ali
Faizuloev, Evgeny
Zverev, Vitaly V.
Svitich, Oxana A.
Nasedkina, Tatiana V.
author_facet Ammour, Yulia
Susova, Olga
Krasnov, George
Nikolaeva, Eugenia
Varachev, Vyacheslav
Schetinina, Yulia
Gavrilova, Marina
Mitrofanov, Alexey
Poletaeva, Anna
Bekyashev, Ali
Faizuloev, Evgeny
Zverev, Vitaly V.
Svitich, Oxana A.
Nasedkina, Tatiana V.
author_sort Ammour, Yulia
collection PubMed
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 MMP3. Thus, such genes could be considered intriguing candidates for further study of factors responsible for cell sensitivity and resistance to L-16 MV infection.
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spelling pubmed-96966242022-11-26 Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus Ammour, Yulia Susova, Olga Krasnov, George Nikolaeva, Eugenia Varachev, Vyacheslav Schetinina, Yulia Gavrilova, Marina Mitrofanov, Alexey Poletaeva, Anna Bekyashev, Ali Faizuloev, Evgeny Zverev, Vitaly V. Svitich, Oxana A. Nasedkina, Tatiana V. Viruses Article 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 MMP3. Thus, such genes could be considered intriguing candidates for further study of factors responsible for cell sensitivity and resistance to L-16 MV infection. MDPI 2022-11-02 /pmc/articles/PMC9696624/ /pubmed/36366531 http://dx.doi.org/10.3390/v14112433 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ammour, Yulia
Susova, Olga
Krasnov, George
Nikolaeva, Eugenia
Varachev, Vyacheslav
Schetinina, Yulia
Gavrilova, Marina
Mitrofanov, Alexey
Poletaeva, Anna
Bekyashev, Ali
Faizuloev, Evgeny
Zverev, Vitaly V.
Svitich, Oxana A.
Nasedkina, Tatiana V.
Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696624/
https://www.ncbi.nlm.nih.gov/pubmed/36366531
http://dx.doi.org/10.3390/v14112433
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