Complex evolutionary dynamics including reassortment drive genome diversity in human rotavirus species A circulating...

Rotavirus A (RVA), belonging to the species Rotavirus alphagastroenteritidis, is among the most frequently diagnosed viral causes of gastroenteritis. The inclusion of RVA vaccines in the primary childhood immunisation schedules of multiple countries has led to significant reductions in yearly-reported cases. Nevertheless, such interventions may exert selective pressures that could result in the emergence of novel vaccine escape variants. RVA classification has traditionally focused on two of eleven gene segments encoding the capsid proteins, VP4 and VP7, which limits evolutionary assessments of genomic diversity and reassortments involving the other segments. A viral metagenomics approach (NetoVIR) was employed to investigate the genomic diversity of RVA in Ireland. The analysis focused on clinical samples (n = 140) collected from patients between 2015 and 2021. Besides the Wa-like or DS-1-like genotype constellations, 4/140 genomes (3 %) were identified as reassortant, with an NSP2 genotype 1 in a DS-1-like constellation. Also, we confirmed the circulation of OP354-like P[8] strains in six G9P[8] samples. Notably, these strains show dissimilarity in the antigenic epitopes of the VP4 protein compared to the Rotarix vaccine. Furthermore, we detected strains with an equine-like G3 (EQL-G3) VP7 gene within a DS-1-like constellation (n = 5/140, 4 %) and the unusual combination of G1P[8] with a DS-1-like constellation in 6/22 (27 %) of the G1P[8] samsples. Our study supports using a viral metagenomic approach for RVA genetic characterisation to determine pathogen diversity and reassortments. The public health implications of the identified reassortant RVA strains, requires investigations for any potential impacts on vaccine efficacies.