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The NS2B-PP1α-eIF2α axis: Inhibiting stress granule formation and Boosting Zika virus replication.
- Source :
- PLoS Pathogens, Vol 20, Iss 6, p e1012355 (2024)
- Publication Year :
- 2024
- Publisher :
- Public Library of Science (PLoS), 2024.
-
Abstract
- Stress granules (SGs), formed by untranslated messenger ribonucleoproteins (mRNPs) during cellular stress in eukaryotes, have been linked to flavivirus interference without clear understanding. This study reveals the role of Zika virus (ZIKV) NS2B as a scaffold protein mediating interaction between protein phosphatase 1α (PP1α) and eukaryotic initiation factor 2α (eIF2α). This interaction promotes eIF2α dephosphorylation by PP1α, inhibiting SG formation. The NS2B-PP1α complex exhibits remarkable stability, resisting ubiquitin-induced degradation and amplifying eIF2α dephosphorylation, thus promoting ZIKV replication. In contrast, the NS2BV35A mutant, interacting exclusively with eIF2α, fails to inhibit SG formation, resulting in reduced viral replication and diminished impact on brain organoid growth. These findings reveal PP1α's dual role in ZIKV infection, inducing interferon production as an antiviral factor and suppressing SG formation as a viral promoter. Moreover, we found that NS2B also serves as a versatile mechanism employed by flaviviruses to counter host antiviral defenses, primarily by broadly inhibiting SG formation. This research advances our comprehension of the complex interplay in flavivirus-host interactions, offering potential for innovative therapeutic strategies against flavivirus infections.
- Subjects :
- Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 15537366 and 15537374
- Volume :
- 20
- Issue :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.b26e3669fd45441f8dd34ffc77c4ed75
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.ppat.1012355