Genome variability and capsid structural constraints of hepatitis a virus

Abstract

The number of synonymous mutations per synonymous site (K(s)), the number of nonsynonymous mutations per nonsynonymous site (K(a)), and the codon usage statistic (N(c)) were calculated for several hepatitis A virus (HAV) isolates. While K(s) was similar to those of poliovirus (PV) and foot-and-mouth disease virus (FMDV), K(a) was 1 order of magnitude lower. The N(c) parameter provides information on codon usage bias and decreases when bias increases. The N(c) value in HAV was about 38, while in PV and FMDV, it was about 53. The emergence of 22 rare codons in front of 8 in PV and 7 in FMDV was detected. Most of the conserved rare codons of the P1 region were strategically located at the carboxy borders of beta barrels and alpha helices, their potential function being the assurance of proper folding of the capsid proteins through a decrease in the translation speed. This strategic location was not observed for amino acids encoded by the conserved rare codons of the 3D region. The percentage of bases with low pairing number values was higher in the latter region, suggesting a role of the conserved rare codons in the maintenance of RNA structure. Many of the rare codons in HAV are among the most frequent in humans, unlike in PV or in FMDV. This fact may be explained by the lack of cellular shutoff in HAV. One hypothesis is that HAV has evolved in order to avoid competition with its host for cellular tRNAs.

FIG. 1.

VP2, VP3, and VP1 structural wire plot models deduced from actual data for PV-1 (Mahoney). (A) VP2. (B) VP3. (C) VP1. The first and second rows correspond to the outbreak and GenBank consensus sequences, respectively. Bold type indicates amino acids encoded by conserved rare codons.

FIG. 2.

Capsid surface location of amino acids encoded by conserved rare codons in an HAV protomer refined model (Luo, personal communication). Green, pink, and blue spheres indicate residues of VP2, VP3, and VP1, respectively, encoded by rare codons. Yellow spheres correspond to residues implicated in antigenic sites.