Complete genome analysis of contemporary G12P[8] rotaviruses reveals heterogeneity within Wa-like genomic constellation

G12 rotaviruses are globally emergent rotaviruses causing severe childhood gastroenteritis. Little is known about the evolution and diversity of G12P[8] rotaviruses and the possible role that widespread vaccine use, globally, has had on their emergence. In Sicily, Italy, surveillance activity for rotaviruses has been conducted uninterruptedly since 1985, thus representing a unique observatory for the study of human rotaviruses in the pre- and post-vaccine era. G12 rotaviruses were first detected only in 2012 and between 2012 and 2014 they accounted for 8.7% of all rotavirus-associated infections among children, with peaks of 27.8% in 2012/2013 and 21% in 2014. We determined and analyzed the full-genome of 22 G12P[8] rotaviruses collected during the 2012-2014. Although all G12P[8] rotaviruses exhibited a typical Wa-like genotype constellation (G12P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1), phylogenetic analysis allowed distinguishing either two or three (sub)lineages in each genome segment. On the basis of the segregation patterns into lineages/sublineages, 20 G12P[8] rotaviruses could be grouped into three stable major genomic sub-constellations, whilst two strains displayed unique genome architectures, likely due to ressortment with co-circulating strains. Altogether, these findings indicate that the onset and prolonged circulation of G12 rotaviruses was due to repeated introductions of different G12 rotaviruses circulating globally. Importantly, as regional rotavirus vaccination was initiated in 2012 reaching a 45% coverage in newborns in 2014, a correlation between the appearance and spread of G12 rotaviruses and the enacted vaccination program could not be drawn. Constant epidemiologic surveillance remains important to monitor the epidemiological dynamics of human rotaviruses.