Mwangi, Peter N.Page, Nicola AnneSeheri, Mapaseka L.Mphahlele, M.Nadan, SandramaEsona, Mathew D.Kumwenda, BenjaminKamng’ona, Arox W.Donato, Celeste M.Steele, Duncan A.Ndze, Valantine N.Dennis, Francis E.Jere, Khuzwayo C.Nyaga, Martin M.2023-09-182023-09-182022-04Mwangi, P.N., Page, N.A., Seheri, M.L. et al. 2022, 'Evolutionary changes between pre- and post-vaccine South African group A G2P[4] rotavirus strains, 2003–2017', Microbial Genomics, vol. 2022, no. 8, pp. 1-14. DOI 10.1099/mgen.0.000809.2057-585810.1099/mgen.0.000809http://hdl.handle.net/2263/92310DATA STATEMENT : All supporting data, code and protocols have been provided within the article or through supplementary data files.The transient upsurge of G2P[4] group A rotavirus (RVA) after Rotarix vaccine introduction in several countries has been a matter of concern. To gain insight into the diversity and evolution of G2P[4] strains in South Africa pre- and post-RVA vaccination introduction, whole-genome sequencing was performed for RVA positive faecal specimens collected between 2003 and 2017 and samples previously sequenced were obtained from GenBank (n=103; 56 pre- and 47 post-vaccine). Pre-vaccine G2 sequences predominantly clustered within sub-lineage IVa-1. In contrast, post-vaccine G2 sequences clustered mainly within sub-lineage IVa-3, whereby a radical amino acid (AA) substitution, S15F, was observed between the two sub-lineages. Pre-vaccine P[4] sequences predominantly segregated within sub-lineage IVa while post-vaccine sequences clustered mostly within sub-lineage IVb, with a radical AA substitution R162G. Both S15F and R162G occurred outside recognised antigenic sites. The AA residue at position 15 is found within the signal sequence domain of Viral Protein 7 (VP7) involved in translocation of VP7 into endoplasmic reticulum during infection process. The 162 AA residue lies within the hemagglutination domain of Viral Protein 4 (VP4) engaged in interaction with sialic acid-containing structure during attachment to the target cell. Free energy change analysis on VP7 indicated accumulation of stable point mutations in both antigenic and non-antigenic regions. The segregation of South African G2P[4] strains into pre- and post-vaccination sub-lineages is likely due to erstwhile hypothesized stepwise lineage/sub-lineage evolution of G2P[4] strains rather than RVA vaccine introduction. Our findings reinforce the need for continuous whole-genome RVA surveillance and investigation of contribution of AA substitutions in understanding the dynamic G2P[4] epidemiology.en© 2022 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License.G2P[4] Group A rotavirus strainsRotavirusSub-lineagesWhole-genome analysisArticle