Evolutionary changes between pre- and post-vaccine South African group A G2P[4] rotavirus strains, 2003-2017

Peter N. Mwangi, Nicola A. Page, Mapaseka L. Seheri, M. Jeffrey Mphahlele, Sandrama Nadan, Mathew D. Esona, Benjamin Kumwenda, Arox W. Kamng'ona, Celeste M. Donato, Duncan A. Steele, Valantine N. Ndze, Francis E. Dennis, Khuzwayo C. Jere, Martin M. Nyaga

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalMicrobial genomics
Volume8
Issue number4
DOIs
Publication statusPublished - 1 Apr 2022

Keywords

  • G2P[4] group A rotavirus strains
  • rotavirus
  • sub-lineages
  • whole-genome analysis

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