The codon usage code for co-translational folding of viral capsids.

Codon bias is common to all organisms and is the result of mutation, drift, and selection. Selection for the efficiency and accuracy of translation is well recognized as a factor shaping the codon usage. In contrast, fewer studies report the control of the rate of translation as an additional selective pressure influencing the codon usage of an organism. Experimental molecular evolution using RNA virus populations is a powerful tool for the identification of mechanisms underlying the codon bias. Indeed, the role of deoptimized codons on the co-translational folding has been proven in the capsids of two fecal-orally transmitted picornaviruses, poliovirus and the hepatitis A virus, emphasizing the role of the frequency of codons in determining the phenotype. However, most studies on virus codon usage rely only on computational analyses, and experimental studies should be encouraged to clearly define the role of selection on codon evolution.