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| Main Authors: | , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Frontiers in cellular and infection microbiology
2024
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39679197/ |
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Table of Contents:
- ZIKV prM hijacks PIM1 kinase for phosphorylation to prevent ubiquitin-mediated degradation and facilitate viral replication. Ren, Yingying Liu, Yishuo Pang, Rui Xu, Gang Lei, Yining Kwok, Hang Fai Wu, Yingliang Cao, Zhijian Proto-Oncogene Proteins c-pim-1 Animals Virus Replication Phosphorylation Zika Virus Mice Humans Proteolysis Ubiquitin Zika Virus Infection Host-Pathogen Interactions HEK293 Cells Ubiquitination Ubiquitin-Protein Ligases Vero Cells Chlorocebus aethiops Imidazoles Pyridazines Viral infection usually stimulates a variety of host cell factors to modulate the life cycle of the virus. PIM1, a serine/threonine protein kinase widely involved in cell proliferation, survival, differentiation and apoptosis, was recently reported to be upregulated by Zika virus (ZIKV) infection. However, how ZIKV-PIM1 interactions affect the viral life cycle are not fully understood. Here, we demonstrated that ZIKV replication was suppressed by the PIM1 kinase inhibitor SGI-1776 in both and murine peritoneal macrophages, indicating that PIM1 functions independently of type I IFN signaling. Co-immunoprecipitation and GST pull-down assays revealed that the ZIKV structural protein precursor membrane (prM) interacted with PIM1. Moreover, we found that prM protein stability was enhanced by PIM1, which was attributed to its kinase activity. Mechanistically, we revealed that prM can undergo ubiquitin‒mediated proteolysis and the E3 ubiquitin ligase AMFR can target prM for degradation. Importantly, PIM1 catalyzed phosphorylation of prM at Ser101 and Thr107, and this phosphorylation prevented the proteasome-dependent degradation of prM by impairing its association with AMFR. Therefore, the S101/T107-D phosphorylation mimic mutant of prM was more resistant to PIM1-induced increases in cellular abundance. These findings revealed PIM1 as a critical host factor that is advantageous to ZIKV and revealed that targeting the PIM1‒prM axis is a conducive strategy for controlling ZIKV infection.