Temporal fluctuations of G4P[8] rotaviruses do not correlate with changes in the VP7 antigenic regions.

By monitoring the circulation of group A rotaviruses (RV) in children hospitalized with diarrhoea in Parma, Northern Italy, during 2004-2005 and 2008-2010, G1P[8] RVs were predominant, while marked fluctuations were observed for other RV strains, chiefly for G4P[8] viruses. In 2004 and 2010, G4P[8] displayed prevalence peaks (15.19% and 19.58%, respectively), whereas in 2005 and 2008 they circulated at low rate (0.1% and 2.1%, respectively). In order to gain further insights into the genetic diversity and evolution of G4P[8] RVs, 19 strains were selected for sequencing of the VP7 and VP4 genome segments. Upon molecular analyses, all the G4P[8] strains possessed a VP7 of 1C sublineage and a VP4 of P[8]-III lineage. All the strains were highly conserved in the VP7 gene, sharing a high degree of nucleotide and amino acid similarities to VP7 sequences of G4 strains detected worldwide. Conversely, two distinct P[8]-III sublineages were identified by analysing the VP8* subunit of the VP4 gene. One minor sublineage included strains detected in 2004, while the other cluster included strains detected in 2005, 2009 and 2010. The former major lineage displayed several amino acid changes (37-Pro, 85-Thr, 95-Ser and 135-Asn). Accordingly, the observed fluctuations in G4P[8] prevalence over the years did not correlate with changes in the major antigenic sites of the VP7 capsid protein, while several mutations were mapped in the hypervariable region VP8* of the VP4. The P[8] specificity is the most common type in human RVs worldwide and this antigenic type is present in both the human vaccines available in the market. A marked genetic heterogeneity has been observed within the P[8] type and this could be associated with the worldwide predominance of P[8] viruses. Whether the onset and replacement of different P[8] lineages and sublineages reflect a mechanism used by P[8] RVs to escape from the herd immunity acquired by local population raised to previous RV strains is an interesting hypothesis that fit the picture portrayed in this study and in similar investigations.