Sarah Esstman, Wake Forest

Linford L. Otoo and Sarah M. Esstman, Department of Biology, Wake Forest University

Epidemiology, Evolution, and Diversity

Human group A rotaviruses (RVAs) typically belong to one of two genogroups with distinct genotype constellations: (i) Wa-like genogroup strains exhibit Gx-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 constellations, while (ii) DS-1-like genogroup strains exhibit Gx-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 constellations. Historically, reassortant strains containing a mix of genotypes from each genogroup were rarely identified as causes of acute gastroenteritis in children. However, since 2013, there has been a worldwide emergence of intergenogroup reassortants that exhibit Wa-like P[8] VP4 genes in an otherwise DS-1-like genetic backbone (P[8]DS-1). In this study, we sought to determine whether these emergent P[8]DS-1 reassortants were genetically distinct from typical P[4] VP4-containing DS-1-like (P[4]DS-1) strains. We analyzed the genome sequences of 80 P[8]DS-1 reassortants and 54 P[4]DS-1 control strains collected between the years 2012-2022 from symptomatic children in 19 countries. Nucleotide sequence alignments and neighbor-joining phylogenetic trees were constructed for each viral gene. The results showed that the VP1-VP3, VP6, and NSP1-NSP4 genes of most P[8]DS-1 reassortants clustered distinctly from those of most control P[4]DS-1 strains, thereby defining unique alleles in the reassortant viral population. Sequence alignments were then used to identify 286 nucleotide and 34 amino acid changes that differentiated the P[8]DS-1 reassortants from typical P[4]DS-1 strains. Ongoing work seeks to understand if/how these unique genetic signatures influenced the emergence of P[8]DS-1 reassortant strains over the past 10+ years.