Association of EV71 3C polymorphisms with clinical severity

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Enterovirus 71 (EV71) is a significant pathogen causing severe neurological disease and fatalities.
• The EV71 3C protein is crucial for viral replication and possesses protease activity, suggesting a role in pathogenesis.

Purpose of the Study:

• To investigate the genetic variations of EV71 3C.
• To analyze the correlation between 3C genetic polymorphisms, protease activity, viral replication, and clinical severity.
• To explore the interaction of EV71 3C with host proteins.

Main Methods:

• Sequencing of EV71 3C gene from clinical cases and correlation with disease severity.
• Analysis of 3C protease activity and viral replication rates using EV71 infectious clones.
• Investigation of 3C interaction with host proteins, including TRIM21.

Main Results:

• Polymorphisms in EV71 3C, specifically at the 79th amino acid, are strongly associated with clinical severity.
• EV71 strains with a mutant 3C (T79V) showed significantly higher rates of neurological involvement (78%) compared to wild-type (26%).
• Mutant 3C (T79V) exhibited higher viral replication rates and weaker interaction with TRIM21, a key host factor in viral defense.

Conclusions:

• EV71 3C genetic variations are linked to differences in clinical outcomes and viral replication efficiency.
• The altered interaction of mutant 3C with host proteins like TRIM21 may contribute to increased EV71 virulence and pathogenesis.