Detection of recombination breakpoints in the genomes of human enterovirus 71 strains isolated in the Netherlands in epidemic and non-epidemic years, 1963-2010.

Evolutionary history of human enterovirus 71 (EV71) in the Netherlands shows displacement of virus subgenogroups, that only partly can be explained by antigenic changes. Additionally, occasional epidemics have occurred that remain to be explained. Previous studies have shown subgenogroup specific recombination events in the genome of Asian EV71 strains. To find clues on the role of genome recombination in evolution of the EV71 subgenogroups found in Europe and in the evolution of strains capable of causing outbreaks, we analyzed the genomes of 19 strains representing the genetic diversity of EV71 in the Netherlands between 1963 and 2010. We selected viruses from EV71 endemic and epidemic years (1986 and 2007). Subgenogroup specific genome recombination events were detected for subgenogroup B0, B1 and B2 viruses, in line with observed genome recombination events in Asian subgenogroup B3 and B4 viruses. Considering recombination events distinguishing strains from epidemic years from those of non-epidemic years, breakpoints for recombination were detected in the 5'UTR of B2 viruses from the outbreak in 1986, with highest similarity of the 5'UTR to B4 and B3 strains isolated during outbreaks in the Asian Pacific region. No indications for recombination were found in genogroup C isolates. Except for the '86 B2 isolates' Dutch isolates phylogenetically interspersed with international reference strains of the same subgenogroup, indicating a global dissemination of (recombinant) EV71 viruses. The difference observed in the 5'UTR of EV71 strains isolated in endemic versus epidemic years suggests that changes in the 5'UTR cause evolution of strains capable of causing outbreaks.