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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 [PLoS Pathog] 2020 Jun 30; Vol. 16 (6), pp. e1008610. Date of Electronic Publication: 2020 Jun 30 (Print Publication: 2020). - 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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Chick Embryo
Chickens
HEK293 Cells
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins genetics
Intracellular Signaling Peptides and Proteins metabolism
Nucleocapsid Proteins
Phosphatidylinositol 3-Kinases genetics
Phosphatidylinositol 3-Kinases metabolism
Protein Biosynthesis
Protein Serine-Threonine Kinases genetics
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins c-akt genetics
Proto-Oncogene Proteins c-akt metabolism
TOR Serine-Threonine Kinases genetics
TOR Serine-Threonine Kinases metabolism
p38 Mitogen-Activated Protein Kinases genetics
p38 Mitogen-Activated Protein Kinases metabolism
Avian Proteins genetics
Avian Proteins metabolism
Eukaryotic Initiation Factor-4E genetics
Eukaryotic Initiation Factor-4E metabolism
MAP Kinase Signaling System
Newcastle disease virus genetics
Newcastle disease virus metabolism
Nucleoproteins biosynthesis
Nucleoproteins genetics
Nucleoproteins metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
RNA, Viral genetics
RNA, Viral metabolism
Viral Proteins biosynthesis
Viral Proteins genetics
Viral Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 16
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 32603377
- Full Text :
- https://doi.org/10.1371/journal.ppat.1008610