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.