Key result
Hepatitis A virus utilizes highly biased and deoptimized codon usage to avoid competition for host tRNAs and slow translation elongation, which intrinsically modulates capsid folding.
HAV codon usage deoptimization slows translation elongation to modulate capsid folding, providing a paradigmatic example of a codon usage code for protein structure.
Exemplifies codon deoptimization modulating viral capsid folding; leaves open applications to vaccine design or other pathogens.
Codon usage bias is universal to all genomes. Hepatitis A virus (HAV) codon usage is highly biased and deoptimized with respect to its host. Accordingly, HAV is unable to induce cellular translational shutoff and its internal ribosome entry site (IRES) is inefficient. Codon usage deoptimization may be seen as a hawk (host cell) versus dove (HAV) game strategy for accessing transfer RNA (tRNA). HAV avoids use of abundant host cell codons and thereby eludes competition for the corresponding tRNAs. Instead, codons that are abundant or rare in cellular messenger RNAs (mRNAs) are used relatively rarely in its genome, although intermediately abundant host cell codons are abundant in the viral genome. Rare codons in the capsid coding region slow down the translation elongation rate, and in doing so intrinsically modulate capsid folding, which is critical to the stability of a virus transmitted through the fecal-oral route. HAV is a paradigmatic example of what has been proposed as a codon usage "code" for protein structure.
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Pintó et al. (2018) conducted a review in Hepatitis A virus. Hepatitis A virus codon usage was evaluated. Hepatitis A virus utilizes highly biased and deoptimized codon usage to avoid competition for host tRNAs and slow translation elongation, which intrinsically modulates capsid folding.
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