Enterovirus D68 Sequence Variations and Pathogenicity: A Review

Area of Science:

• Virology
• Genomics
• Epidemiology

Background:

• Enterovirus D68 (EV-D68) is a neurotropic respiratory virus linked to pediatric acute flaccid myelitis (AFM) and severe respiratory illness.
• Recurrent epidemics of EV-D68, noted since 2014, highlight the need to understand its virulence factors.
• Genomic determinants significantly modify EV-D68 pathogenicity by affecting host interactions, immune evasion, and replication.

Purpose of the Study:

• To systematically review genomic sites that enhance EV-D68 virulence.
• To focus on critical regions: VP1 receptor-binding site, 2Apro/TRAF3 cleavage site, and 3Cpro immunoregulatory region.
• To propose monitoring key virulence determinants for outbreak preparedness.

Main Methods:

• Systematic literature review of genomic variations in EV-D68.
• Analysis of mutations in VP1, 2Apro/TRAF3, and 3Cpro regions.
• Correlation of sequence variations with host-receptor interactions, immune evasion, and replication efficiency.

Main Results:

• Mutations in the VP1 site alter affinity for host receptors (sialic acid, heparan sulfate, MFSD6), impacting viral entry and tropism.
• Alterations in the 2Apro/TRAF3 cleavage site may reduce immune evasion by impairing TRAF3 cleavage, thus decreasing pathogenicity.
• Variations in the 3Cpro region modulate viral replication and antiviral responses by affecting cleavage of host proteins involved in translation and autophagy.

Conclusions:

• Specific genomic sites, including VP1, 2Apro/TRAF3, and 3Cpro, are critical for EV-D68 virulence.
• Monitoring mutations in these regions, especially the surface-exposed VP1, is essential for effective outbreak preparedness.
• Understanding genomic determinants of EV-D68 virulence can improve strategies for managing and preventing epidemics.