EV71 5'UTR interacts with 3D protein affecting replication through the AKT-mTOR pathway.

Area of Science:

• Virology
• Molecular Biology
• Cellular Biology

Background:

• Enterovirus 71 (EV71) is a significant cause of Hand-foot-and-mouth disease (HFMD), often leading to severe neurological complications.
• Previous research suggested a potential interaction between the EV71 5' untranslated region (5'UTR) and the 3D protein, but its role in viral replication remained unclear.

Purpose of the Study:

• To investigate the interaction between the EV71 5'UTR and the 3D protein.
• To determine the impact of this interaction on viral replication and host cell autophagy.

Main Methods:

• Mutagenesis of four 5'UTR sites and two 3D protein sites in virulent EV71 strains.
• Analysis of mutant virus replication and their effects on cellular autophagy.
• Assessment of the autophagy pathway, including autophagosome accumulation, autolysosome degradation, and AKT/mTOR signaling.

Main Results:

• Single 5'UTR mutations, except for one, attenuated viral replication compared to the virulent parent strain.
• Co-mutant strains exhibited varied replication characteristics, with five showing evidence of interaction.
• High-replicative strains promoted autophagosome accumulation, hindered autolysosome degradation, and inhibited AKT/mTOR phosphorylation.
• Low-replicative strains showed minimal regulation of host cell autophagy.

Conclusions:

• The EV71 5'UTR interacts with the 3D protein, influencing viral replication.
• Specific co-mutations (S37N-nt88C/T, S37N-nt574T/A, R142K-nt574T/A) promote viral replication by inhibiting the AKT-mTOR autophagy pathway.
• Other co-mutations (R142K-nt88C/T, R142K-nt157G/A) reduce viral replication by lessening the inhibition of the AKT-mTOR pathway.