학술논문
Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus.
Document Type
Academic Journal
Author
Ammour Y; I.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, Russia.; Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 119991 Moscow, Russia.; Susova O; N.N. Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation, 115478 Moscow, Russia.; Krasnov G; Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 119991 Moscow, Russia.; Nikolaeva E; I.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, Russia.; Varachev V; Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 119991 Moscow, Russia.; Schetinina Y; I.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, Russia.; Gavrilova M; I.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, Russia.; Mitrofanov A; N.N. Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation, 115478 Moscow, Russia.; Poletaeva A; N.N. Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation, 115478 Moscow, Russia.; Bekyashev A; N.N. Blokhin Russian Cancer Research Center of the Ministry of Health of the Russian Federation, 115478 Moscow, Russia.; Faizuloev E; I.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, Russia.; Zverev VV; I.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, Russia.; Department of Microbiology, Virology and Immunology of the Medical and Preventive Faculty, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, 119146 Moscow, Russia.; Svitich OA; I.I. Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, Russia.; Department of Microbiology, Virology and Immunology of the Medical and Preventive Faculty, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, 119146 Moscow, Russia.; Nasedkina TV; Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 119991 Moscow, Russia.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
Subject
Language
English
Abstract
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.