P300-mediated NEDD4 acetylation drives ebolavirus VP40 egress by enhancing NEDD4 ligase activity

The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize...

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Bibliographic Details
Published in:PLoS pathogens 2021-06, Vol.17 (6), p.e1009616-e1009616
Main Authors: Zhang, Linliang, Zhou, Shixiong, Chen, Majuan, Yan, Jie, Yang, Yi, Wu, Linjuan, Jin, Dongning, Yin, Lei, Chen, Mingzhou, Qin, Yali
Format: Article
Language:English
Subjects:
Acetylation
Acetyltransferase
Antibodies
Biology and Life Sciences
Budding
Cell lines
Ebola virus
Ebolavirus
Egress
Genetic aspects
Hypotheses
Life cycles
Ligases
Mass spectrometry
Matrix protein
Medicine and Health Sciences
Phosphorylation
Physical Sciences
Physiological aspects
Physiological effects
Plasmids
Post-translation
Post-translational modification
Proteins
Regulatory mechanisms (biology)
Research and Analysis Methods
Scientific imaging
Transcriptional coactivators
Ubiquitin-proteasome system
Ubiquitin-protein ligase
Ubiquitination
Viral infections
Virus research
Viruses
VP40 protein
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Summary:The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize NEDD4 is acetylated at a conserved Lys667 mediated by the acetyltransferase P300 which drives VP40 egress process. Importantly, P300-mediated NEDD4 acetylation promotes NEDD4-VP40 interaction which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. Finally, we find that Zaire ebolavirus production is dramatically reduced in P300 knockout cell lines, suggesting that P300-mediated NEDD4 acetylation may have a physiological effect on Ebola virus life cycle. Thus, our study identifies an acetylation-dependent regulatory mechanism that governs VP40 ubiquitination and provides insights into how acetylation controls EBOV VP40 egress.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1009616