Phylogenetic Analysis of Rubella Viruses Involved in Congenital Rubella Infections in France between 1995 and 2009

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Abstract
Rubella is an acute infectious disease that normally has a mild clinical course. However, infections during pregnancy, especially before week 12 of gestation (WG), can cause severe birth defects known as congenital rubella syndrome (CRS). The aim of this study was to perform genotyping and molecular characterization of rubella viruses involved in congenital infections in France over the past 15 years (1995 to 2009). Amniotic fluid (AF) specimens ( n = 80) from pregnant women with congenital rubella infections (CRI) before week 20 of gestation, and a few other samples available from children/newborns with CRS ( n = 26), were analyzed. The coding region of the rubella virus E1 gene was amplified directly from clinical specimens by reverse transcriptase PCR, and the resulting DNA fragments were sequenced. Sequences were assigned to genotypes by phylogenetic analysis with rubella virus reference sequences. Sufficient E1 gene sequences were obtained from 56 cases. Phylogenetic analysis of the sequences showed that at least five different genotypes (1E, 1G, 1B, 2B, and 1h) were present in France and were involved in congenital infections, with a strong predominance of genotype 1E (87%). This is one of the very few comprehensive studies of rubella viruses involved in CRI. The results indicated that over the past 15 years, multiple introductions of the dominant genotype E caused most of the CRI cases in France. A few sporadic cases were due to other genotypes (1B, 1G, 1h, 2B).