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Newcastle Disease virus infection activates PI3K/Akt/mTOR and p38 MAPK/Mnk1 pathways to benefit viral mRNA translation via interaction of the viral NP protein and host eIF4E.
- Source :
- PLoS Pathogens; 6/30/2020, Vol. 16 Issue 6, p1-28, 28p
- Publication Year :
- 2020
-
Abstract
- Newcastle disease virus (NDV), a member of the Paramyxoviridae family, can activate PKR/eIF2α signaling cascade to shutoff host and facilitate viral mRNA translation during infection, however, the mechanism remains unclear. In this study, we revealed that NDV infection up-regulated host cap-dependent translation machinery by activating PI3K/Akt/mTOR and p38 MAPK/Mnk1 pathways. In addition, NDV infection induced p38 MAPK/Mnk1 signaling participated 4E-BP1 hyperphosphorylation for efficient viral protein synthesis when mTOR signaling is inhibited. Furthermore, NDV NP protein was found to be important for selective cap-dependent translation of viral mRNAs through binding to eIF4E during NDV infection. Taken together, NDV infection activated multiple signaling pathways for selective viral protein synthesis in infected cells, via interaction between viral NP protein and host translation machinery. Our results may help to design novel targets for therapeutic intervention against NDV infection and to understand the NDV anti-oncolytic mechanism. Author summary: Viruses are obligate intracellular parasites and have no protein translation machinry of their own. Therefore, viruses remain exclusively dependent on host translation machinery to ensure viral protein synthesis and progeny virion production during infection. We previous reported that Newcastle disease virus (NDV) shutoff host and facilitate viral mRNA translation by activating PKR/eIF2α signaling cascade. Here, we demonstrated that NDV infection up-regulated host cap-dependent translation machinery by activating PI3K/Akt/mTOR and p38 MAPK/Mnk1 pathways. Furthermore, NDV NP protein was found to be important for selective cap-dependent translation of viral mRNAs. Our findings highlight a new strategy how virus used host translation machinery for selective viral protein synthesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 16
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 144320443
- Full Text :
- https://doi.org/10.1371/journal.ppat.1008610