Phylogenetic analysis of rubella virus including new genotype I isolates

Infection during the first trimester of gestation with rubella virus (RV) is highly teratogenic. Embryopathy is a frequent outcome of the primary natural infection with wild type RV during pregnancy while accidental immunisation with life attenuated vaccine has apparently little or no adverse effect. Although the nucleic acid sequence of RV is exceptionally stable, differences between the vaccine and wild type viruses could play a role in the pathogenesis of intrauterine RV infection. Phylogenetic analysis of eight complete sequences (including two new isolates described in this paper, three vaccine strains, three cell culture adapted wild type viruses) confirms a striking low divergence of the RV genome. A variable region (amino acid residues 697-800) within the gene coding for the nonstructural protein NSP1 was defined. Phylogenetic analysis revealed a strong positive selection in this region. Multiple passages in vivo or in vitro did not account for this variability. As the function of the variable region has not yet been elucidated, reasons for and significance of positive selection are still speculative. It is conceivable that the variable region in NSP1 contributes to the molecular basis of RV embryopathy and other complications of postnatal RV infection.