Heterogeneity and temporal dynamics of evolution of G1 human rotaviruses in a settled population

Abstract

A rotavirus sample collection from 19 consecutive years was used to investigate the heterogeneity and the dynamics of evolution of G1 rotavirus strains in a geographically defined population. Phylogenetic analysis of the VP7 gene sequences of G1P[8] human rotavirus strains showed the circulation of a heterogeneous population comprising three lineages and seven sublineages. Increases in the circulation of G1 rotaviruses were apparently associated with the introduction of novel G1 strains that exhibited multiple amino acid changes in antigenic regions involved in rotavirus neutralization compared to the strains circulating in the previous years. The emergence and/or introduction of G1 antigenic variants might be responsible for the continuous circulation of G1 rotaviruses in the local population, with the various lineages and sublineages appearing, disappearing, or cocirculating in an alternate fashion under the influence of immune-pressure mechanisms. Sequence analysis of VP4-encoding genes of the G1 strains revealed that the older strains were associated with a unique VP4 lineage, while a novel VP4 lineage emerged after 1995. The introduction of human rotavirus vaccines might alter the forces and balances that drive rotavirus evolution and determine the spread of novel strains that are antigenically different from those included in the vaccine formulations. The continuous emergence of VP7-VP4 gene combinations in human rotavirus strains should be taken into consideration when devising vaccination strategies.

FIG. 1.

Phylogenetic analysis of partial VP7 nucleotide sequences (47 to 1008) of genotype G1 strains. The phylogenetic tree was constructed by the neighbor-joining method and Kimura's two-parameter model, and statistical support was provided by bootstrapping of 1,000 pseudoreplicates. Bootstrap values above 49% are given at branch nodes.

FIG. 2.

Alignment of the VP7 deduced amino acid sequences of Italian G1 strains compared to reference strain Wa. Conserved amino acid residues are indicated by dots.

FIG. 2.

Alignment of the VP7 deduced amino acid sequences of Italian G1 strains compared to reference strain Wa. Conserved amino acid residues are indicated by dots.

FIG. 3.

Phylogenetic analysis of partial VP4 nucleotide sequences (25 to 500) of type P[8] strains. The phylogenetic tree was constructed by the neighbor-joining method and Kimura's two-parameter model, and statistical support was provided by bootstrapping of 1,000 pseudoreplicates. The sequence of P[4] strain PA28 was used as the outgroup. Bootstrap values above 49% are given at branch nodes.

FIG. 4.

Percent temporal distribution of G1 to G4 and G9 types of rotavirus strains circulating in Palermo, Italy, from 1985 to 2004. Arrows indicate the appearance of novel G1P[8] strains named after their VP7 and VP4 sublineages.