Repeated circulation over 6 years of intergenogroup mono-reassortant G2P[4] rotavirus strains with genotype N1 of the NSP2 gene

Abstract

Human rotavirus A, a major cause of acute diarrhoea in infants and young children worldwide, contains the genome of 11 segments of double-stranded RNA, which is grouped into three major genotype constellations: the Wa genogroup (G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1), the DS-1 genogroup (G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2), and the AU-1 genogroup (G3-P[9]-I3-R3-C3-M3-A3-N3-T3-E3-H3). Recently, a G2P[4] strain detected in Kenya in 1982 was reported to be a nonstructural protein 2 (NSP2) gene mono-reassortant between the Wa and DS-1 genogroups. While NSP2 induces heterotypic antibody responses in children, thereby being the likely target of immune selective pressure, it was not known how frequently these NSP2 mono-reassortants circulated among children. In a previous 10 year epidemiological study, out of 100 G2P[4] rotavirus specimens that were typed into 22 distinct electropherotypes (i.e., strains), RNA-RNA hybridization identified that 12 strains were mono-reassortants involving either the NSP2 or the NSP3 gene. The aim of this study was therefore to determine the nucleotide sequences of all 11 genes of the representative mono-reassortant strain (AU605) and the sequences of the reassorted genes of the other mono-reassortant strains. The genome constellation of AU605 was G2-P[4]-I2-R2-C2-M2-A2-N1-T2-E2-H2, indicating that it was a mono-reassortant strain carrying a Wa-like NSP2 genotype on the DS-1 genogroup background. The reassorted gene of the other 11 strains also had the genotype N1 in the NSP2 gene. Given that electrophoretically-identical rotaviruses represent a single strain, the 12 NSP2 mono-reassortants detected in six rotavirus seasons accounted for 36% (36 of 100) of G2P[4] rotavirus specimens in the 10 year collection. The circulation of NSP2 mono-reassortant strains was observed in epidemic seasons when the G2P[4] genotype was not dominant. Taken together with their repeated occurrence at higher-than-expected frequencies, the identification of NSP2 mono-reassortant G2P[4] strains suggests that such genome constellation may also be viable in nature, and that they circulated less rarely than generally believed.