Whole genome characterisation of DS-1-like G8P[4] rotavirus A strains circulating in South Africa between 2009 and 2021 reveals endemic sub-lineages and evidence of radical epitope changes

Abstract

The sub-Saharan African region bears the highest burden of rotavirus-associated morbidity and mortality, with substantial genetic diversity observed in circulating strains despite vaccine introduction. The G8 genotype, originally predominant in bovine strains, has increasingly become prevalent in humans, suggesting a possible interface of animal-to-human transmission and highlighting its role in African strain diversity. In this study, we performed whole genome sequencing and evolutionary analysis of 21 archival G8P[4] strains collected through gastroenteritis surveillance in South Africa between 2009 and 2021 from children under five years of age. All strains exhibited DS-1-like genome constellations and phylogenetically clustered closely with sub-Saharan African G8P[4] strains across all 11 genome segments. A time-resolved phylogeny indicated the co-circulation of multiple G8 sub-lineages, with specific variants persisting for nearly a decade. The mean evolutionary rate for the G8 lineage V sequences was estimated at 1.49 × 10⁻³ substitutions per site per year, with a time to most common recent ancestor of 1981.8, suggesting long-term endemic divergence. Radical amino acid substitutions were identified in neutralising epitopes of VP4 (11 variations) and VP7 (18 variations) relative to the Rotarix® vaccine strain. These changes may impact antigenicity and immune recognition. These findings within the key antigenic sites of G8P[4] strains may reflect ongoing viral adaptation with potential implications for infectivity and sustained circulation in African regions. Taken together, the findings underscore the significance of continued genomic surveillance to monitor evolution and guide the reassessment, optimisation of current vaccines and the development of future vaccines with broader protective efficacy.