Recombination in circulating enteroviruses

Abstract

Recombination is a well-known phenomenon for enteroviruses. However, the actual extent of recombination in circulating nonpoliovirus enteroviruses is not known. We have analyzed the phylogenetic relationships in four genome regions, VP1, 2A, 3D, and the 5' nontranslated region (NTR), of 40 enterovirus B strains (coxsackie B viruses and echoviruses) representing 11 serotypes and isolated in 1981 to 2002 in the former Soviet Union states. In the VP1 region, strains of the same serotype expectedly grouped with their prototype strain. However, as early as the 2A region, phylogenetic grouping differed significantly from that in the VP1 region and indicated recombination within the 2A region. Moreover, in the 5' NTR and 3D region, only 1 strain of 40 grouped with its prototype strain. Instead, we observed a major group in both the 5' NTR and the 3D region that united most (in the 5' NTR) or all (in the 3D region) of the strains studied, regardless of the serotype. Subdivision within that major group in the 3D region correlated with the time of virus isolation but not with the serotype. Therefore, we conclude that a majority, if not all, circulating enterovirus B strains are recombinants relative to the prototype strains, isolated mostly in the 1950s. Moreover, the ubiquitous recombination has allowed different regions of the enterovirus genome to evolve independently. Thus, a novel model of enterovirus genetics is proposed: the enterovirus genome is a stable symbiosis of genes, and enterovirus species consist of a finite set of capsid genes responsible for different serotypes and a continuum of nonstructural protein genes that seem to evolve in a relatively independent manner.

FIG. 1.

Schematic representation of the enterovirus genome. Genome regions studied are indicated by grey boxes.

FIG. 2.

Phylogenetic tree for the VP1 region (nt 3017 to 3343), created with ClustalX software. Numbers at tree nodes represent the numbers of bootstrap pseudoreplicates that support the group below, determined with NJ (ClustalX) and (in parentheses) ML (PHYLIP DNAML) algorithms. Prototype strains are indicated by an asterisk. The scale bar indicates nucleotide sequence distances. Minor groups discussed in the main text are indicated to the right of braces. Shaded areas show groupings of strains of the same serotype.

FIG. 3.

Phylogenetic tree for the 3D region (nt 5885 to 6481). See the legend to Fig. 2 for details. Shaded areas show groupings of strains isolated mostly in the 1990s (A) and 1980s (B).

FIG. 4.

Phylogenetic tree for the 5′ NTR (nt 337 to 600). See the legend to Fig. 2 for details. The shaded area shows a grouping including a majority of modern strains.

FIG. 5.

Phylogenetic tree for the 2A region (nt 3344 to 3552). See the legend to Fig. 2 for details.