Characterizing Cellular Responses During Oncolytic Maraba Virus Infection
by
Golnoush Hassanzadeh 1, Thet Naing 1,3, Tyson Graber 1
, Seyed Mehdi Jafarnejad 2, David F. Stojdl 1, Tommy Alain 1 and Martin Holcik 1,3,*
Golnoush Hassanzadeh 1, Thet Naing 1,3, Tyson Graber 1, Seyed Mehdi Jafarnejad 2, David F. Stojdl 1, Tommy Alain 1 and Martin Holcik 1,3,*
1
Molecular Biomedicine Program, Children′s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada
2
Centre for Cancer Research and Cell Biology (CCRCB), Queen′s University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK
3
Department of Health Sciences, Carleton University, Ottawa, ON K1S 5B6, Canada
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 580; https://doi.org/10.3390/ijms20030580
Received: 5 December 2018 / Revised: 24 January 2019 / Accepted: 25 January 2019 / Published: 29 January 2019
(This article belongs to the Special Issue Translational Control)
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 eIF2α) 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 eIF2α 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.
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MDPI and ACS Style
Hassanzadeh, G.; Naing, T.; Graber, T.; Jafarnejad, S.M.; Stojdl, D.F.; Alain, T.; Holcik, M. Characterizing Cellular Responses During Oncolytic Maraba Virus Infection. Int. J. Mol. Sci. 2019, 20, 580.
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