Activity-Based Protein Profiling Identifies ATG4B as a Key Host Factor for Enterovirus 71 Proliferation

Area of Science:

• Virology
• Molecular Biology
• Chemical Biology

Background:

• Enterovirus 71 (EV71) causes hand, foot, and mouth disease (HFMD).
• Viral proteases are key to EV71 replication, but host protease roles are unclear.
• Understanding host-pathogen interactions is crucial for combating EV71 outbreaks.

Purpose of the Study:

• To identify host proteases involved in EV71 replication.
• To elucidate the mechanism by which host factors influence EV71 proliferation.
• To explore the utility of activity-based proteomics in studying host-pathogen interactions.

Main Methods:

• Design and synthesis of activity-based probes (ABPs) targeting EV71 3Cprotease.
• Affinity capture and identification of host proteins binding to ABPs.
• Biochemical assays to confirm protease activity of identified host factors.
• Genetic disruption of host factors to assess impact on viral replication in vivo.

Main Results:

• Identified autophagy-related protein 4 homolog B (ATG4B) as a host protease interacting with EV71.
• Demonstrated that ATG4B hydrolytically processes EV71 polyprotein substrates with activity comparable to viral 3Cprotease.
• Confirmed that ATG4B is essential for EV71 replication in vivo.

Conclusions:

• Host protease ATG4B plays a critical role in EV71 replication by processing viral polyproteins.
• This study highlights a novel host-virus interaction essential for EV71 pathogenesis.
• Activity-based proteomics is a powerful strategy for uncovering host factors in viral infections.