Back to Search
Start Over
Activity-Based Protein Profiling Identifies ATG4B as a Key Host Factor for Enterovirus 71 Proliferation.
- Source :
-
Journal of virology [J Virol] 2019 Nov 26; Vol. 93 (24). Date of Electronic Publication: 2019 Nov 26 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Virus-encoded proteases play diverse roles in the efficient replication of enterovirus 71 (EV71), which is the causative agent of human hand, foot, and mouth disease (HFMD). However, it is unclear how host proteases affect viral proliferation. Here, we designed activity-based probes (ABPs) based on an inhibitor of the main EV71 protease (3C <superscript>pro</superscript> ), which is responsible for the hydrolysis of the EV71 polyprotein, and successfully identified host candidates that bind to the ABPs. Among the candidates, the host cysteine protease autophagy-related protein 4 homolog B (ATG4B), a key component of the autophagy machinery, was demonstrated to hydrolytically process the substrate of EV71 3C <superscript>pro</superscript> and had activity comparable to that of the viral protease. Genetic disruption of ATG4B confirmed that the enzyme is indispensable for viral proliferation in vivo Our results not only further the understanding of host-virus interactions in EV71 biology but also provide a sample for the usage of activity-based proteomics to reveal host-pathogen interactions. IMPORTANCE Enterovirus 71 (EV71), one of the major pathogens of human HFMD, has caused outbreaks worldwide. How EV71 efficiently assesses its life cycle with elaborate interactions with multiple host factors remains to be elucidated. In this work, we deconvoluted that the host ATG4B protein processes the viral polyprotein with its cysteine protease activity and helps EV71 replicate through a chemical biology strategy. Our results not only further the understanding of the EV71 life cycle but also provide a sample for the usage of activity-based proteomics to reveal host-pathogen interactions.<br /> (Copyright © 2019 American Society for Microbiology.)
- Subjects :
- 3C Viral Proteases
Autophagy-Related Proteins genetics
Cell Line
Cell Proliferation drug effects
Cysteine Endopeptidases genetics
Cysteine Proteases chemistry
Cysteine Proteases metabolism
Enterovirus A, Human drug effects
Enterovirus A, Human enzymology
Enterovirus A, Human growth & development
Gene Expression Regulation
Gene Knockdown Techniques
Host-Pathogen Interactions physiology
Models, Molecular
Protein Conformation
Proteome
Viral Proteins chemistry
Viral Proteins metabolism
Virus Replication
Autophagy-Related Proteins metabolism
Cell Proliferation physiology
Cysteine Endopeptidases metabolism
Enterovirus A, Human metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 93
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 31554687
- Full Text :
- https://doi.org/10.1128/JVI.01092-19