Replacement and Positive Evolution of Subtype A and B Respiratory Syncytial Virus G-Protein Genotypes From 1997-2012 in South Africa

Background. Of the respiratory syncytial virus (RSV) genotypes previously described in South Africa during 1997-2002, only GA2 and GA5 persisted until 2006, with BA having replaced all previous RSV-B genotypes. This poses the question whether RSV-A is more stable than RSV-B and whether positive selection drives evolution of genotypes. Methods. RSV-positive specimens were randomly selected during 2009-2012, subtyped, sequenced, and compared to RSV recovered from specimens obtained during 1997-2001 and 2006-2009. Bayesian phylogenetic analysis was performed on the G-protein. Results. Phylogenetic analysis indicated that RSV-A genotype GA2 dissolved to form SAA2 (unique to South Africa), NA1 and NA2 (identified in Japan), and ON1 (identified in Canada and having a 72-bp insertion) and that GA5 drifted from 1999-2012 to form 3 subgenotypes (GA5 I-III). RSV-B genotypes all had the 60-bp insertion typical of BA genotypes but clustered into subgenotypes BA8-10. Positive selection was identified in the G-protein of both subtypes, but RSV-A's rate of evolution was slower than that of RSV-B, with the most recent common ancestors dating from 1945 and 1951, respectively. Seven new positively selected sites were identified in South African strains, 2 for RSV-A and 5 for RSV-B. Conclusion. Positive selection drove both RSV-A and -B genotypes to evolve, resulting in replacement of all genotypes over the 15-year study period in South Africa.