Replacement of previously circulating respiratory syncytial virus subtype B strains with the BA genotype in South Africa

Abstract

Respiratory Syncytial Virus (RSV) is a major cause of bronchiolitis and pneumonia in infants, immunocompromised and the elderly in both developed and developing countries. Re-infections are common and G protein variability is one mechanism to overcome herd immunity. This is illustrated by the appearance of the BA genotype with a 60 nucleotide duplication dominating the subtype B genotypes in epidemics worldwide. To investigate the evolution of subtype B in South Africa (SA) since 2002 the genetic variability of the G protein was analyzed in all recent strains isolated over four years (2006-2009) in SA hospitals. Bayesian analysis revealed a replacement of all subtype B genotypes previously identified in SA with the BA genotype since 2006, while subtype A genotypes identified in previous years are still circulating. Compared to BA strains from other countries, the evolutionary rate of the SA BA genotype was shown to be 2.305 x 10-3 nucleotide substitutions/site/year and drift was evident. The most recent common ancestor (MRCA) of the SA BA viruses was determined to date back to 1996. All SA BA isolates clustered with the BA-IV sub genotype and the appearance of new sub-genotypes within this branch may occur if drift continues. Sequencing of the complete G protein of selected SA strains revealed an additional 6 nucleotide deletion. Acquisition of the 60 nucleotide duplication appeared to have improved the fitness of this virus and more recent subtype B strains may need to be included in experimental vaccines to evaluate their efficacy in the current setting of evolved circulating strains.