Hepatitis A Virus Codon Usage: Implications for Translation Kinetics and Capsid Folding

Area of Science:

• Virology
• Molecular Biology
• Genomics

Background:

• Codon usage bias is a universal genomic phenomenon.
• Hepatitis A virus (HAV) exhibits significant codon usage bias, deoptimized relative to its host.
• This deoptimization affects HAV's ability to induce host translational shutoff and limits internal ribosome entry site (IRES) efficiency.

Purpose of the Study:

• To investigate the strategic implications of Hepatitis A virus (HAV) codon usage bias in its interaction with host cells.
• To elucidate how HAV's codon usage influences tRNA availability and translation dynamics.
• To explore the link between codon usage, protein structure modulation, and viral stability.

Main Methods:

• Comparative analysis of HAV codon usage against host cellular messenger RNA (mRNA) codon frequencies.
• Examination of the relationship between codon usage patterns and translation elongation rates.
• Assessment of the impact of rare codons on viral capsid folding and stability.

Main Results:

• HAV preferentially utilizes intermediate host cell codons while avoiding abundant and rare ones, suggesting a 'hawk-dove' game strategy for tRNA access.
• The use of rare codons in the capsid coding region slows translation elongation.
• Slower translation rates intrinsically modulate capsid folding, enhancing viral stability for fecal-oral transmission.

Conclusions:

• HAV's codon usage deoptimization is a sophisticated strategy to manage host resources and ensure viral propagation.
• The observed codon usage patterns directly influence viral protein structure and stability.
• HAV serves as a model for understanding codon usage as a regulatory code influencing protein structure and function.