1. Characterizing Cellular Responses During Oncolytic Maraba Virus Infection
- Author
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Thet Naing, Golnoush Hassanzadeh, Tommy Alain, Seyed Mehdi Jafarnejad, David F. Stojdl, Tyson E. Graber, and Martin Holcik
- Subjects
0301 basic medicine ,viruses ,Eukaryotic Initiation Factor-2 ,bcl-X Protein ,translation ,Catalysis ,Virus ,Article ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,0302 clinical medicine ,XIAP ,IRES ,Protein biosynthesis ,Humans ,Eukaryotic Small Ribosomal Subunit ,eIF5B ,RNA, Messenger ,Physical and Theoretical Chemistry ,Eukaryotic Initiation Factors ,Phosphorylation ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Oncolytic Virotherapy ,eIF2 ,biology ,Bcl-xL ,Organic Chemistry ,Translation (biology) ,General Medicine ,Rhabdoviridae ,Ribosome Subunits, Large, Eukaryotic ,biology.organism_classification ,Virology ,3. Good health ,Computer Science Applications ,Oncolytic virus ,Internal ribosome entry site ,Oncolytic Viruses ,MG-1 ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,030220 oncology & carcinogenesis ,Protein Biosynthesis - Abstract
The rising demand for powerful oncolytic virotherapy agents has led to the identification of Maraba virus, one of the most potent oncolytic viruses from Rhabdoviridae family which displays high selectivity for killing malignant cells and low cytotoxicity in normal cells. Although the virus is readied to be used for clinical trials, the interactions between the virus and the host cells is still unclear. Using a newly developed interferon-sensitive mutant Maraba virus (MG1), we have identified two key regulators of global translation (4E-BP1 and eIF2&alpha, ) as being involved in the regulation of protein synthesis in the infected cells. Despite the translational arrest upon viral stress, we showed an up-regulation of anti-apoptotic Bcl-xL protein that provides a survival benefit for the host cell, yet facilitates effective viral propagation. Given the fact that eIF5B canonically regulates 60S ribosome subunit end joining and is able to replace the role of eIF2 in delivering initiator tRNA to the 40S ribosome subunit upon the phosphorylation of eIF2&alpha, we have tested whether eIF5B mediates the translation of target mRNAs during MG1 infection. Our results show that the inhibition of eIF5B significantly down-regulates the level of Bcl-xL steady-state mRNA, thus indirectly attenuates viral propagation.
- Published
- 2019