Phylogenetic analysis of VP7 and VP4 genes of the most predominant human group A rotavirus G12 identified in children with acute gastroenteritis in Himachal Pradesh, India during 2013-2016

G12 strains are now considered to be the sixth most prevalent human rotaviruses globally. India has introduced rotavirus vaccine Rotavac (R) into the national immunization program in 2016 and Himachal Pradesh (HP) is the first state to launch it. During epidemiological rotavirus surveillance in HP, predominance of G12 rotaviruses was observed. This study investigated the genetic variability and evolution of HP G12 strains (n = 15) associated with P-genotypes P[6], P[4], and P[8] identified between 2013 and 2016. Phylogenetic analysis of VP7 gene revealed that all characterized G12 strains clustered in lineage-III and diversified into three subclusters indicating that these strains may have originated from three different ancestral G12 strains. The comparative sequence analysis of HP strains with Rotavac (R) and Rotarix (R) vaccine strains revealed various amino acid substitutions in epitope regions of VP7 and VP4 proteins especially at the antibody neutralization sites. Only 12/29 VP7 epitope residues and 2/25 VP4 epitope residues were found to be conserved between HP rotavirus strains and vaccine strains. Both long and short electropherotypes were observed in G12P[4] strains, while a single long electropherotype was observed in G12P[6] strains. Children of <= 11 months were significantly infected with G12 rotaviruses. The frequency of vomiting episodes (>= 5/day) was significantly higher in children infected with G12 rotavirus strains as compared to non-G12 rotaviruses (p = 0.0405). Our study provides the comprehensive data on clinical characteristics and evolutionary pattern of the G12 rotavirus, the most prevalent strain in HP and emphasizes the need to monitor these strains for inclusion in future vaccine.