Whole-genome analysis of rotavirus G1P[8] and other Wa-like strains in Mozambican children: evidence of genetic variations of pre-vaccine G1P[8] strains from Manhiça, Mozambique

The Rotarix® (GlaxoSmithKline, Rixenstart, Belgium) vaccine was adopted into the Expanded Program on Immunization in Mozambique in September 2015, and G1P[8] strains were frequent pre- and post-vaccine introduction in some regions of the country. In the current study, G1P[8] and other strains (G12P[6], G12P[8] and G9P[8]) circulating between 2008-2012 and 2015 in children with and without diarrhoea were characterized by next-generation sequencing to understand their genetic composition. The G1P[8] strains were compared with Mozambican pre- and post-vaccine strains retrieved from GenBank. All study strains, either from children with or without diarrhoea, were genetically similar and exhibited a typical Wa-like constellation. The Mozambican pre- and post-vaccine G1 strains clustered in two separate lineages: most pre-vaccine strains in lineage I and all post-vaccine strains in lineage II. Meanwhile, all P[8] were in lineage III, although the study strains were in a different cluster from the G1P[8] post-vaccine strains retrieved in GenBank. Analysis of VP7 epitope regions showed amino acid differences such as S123N and M217T in all study strains, while a change N94S was observed in seven strains and K291R in eight strains. Sequence alignment of G1P[8] study strains using mVISTA confirmed that they may have suffered point mutations in all their 11 segments. Our results suggest that host factors are implicated in the inducement and severity of diarrhoea and these factors need further investigation. The changes in some G1 strains at the epitope region emphasize the need for continued whole-genome analysis, as substitutions in this region are reported to affect protein conformation at given positions and the study results may provide data for future studies aiming to understand rotavirus strain evolution post-vaccine introduction.