McDonald SM, McKell AO, Rippinger CM, McAllen JK, Akopov A, Kirkness EF, Payne DC, Edwards KM, Chappell JD, Patton JT
Diversity and Relationships of Co-circulating Modern Human Rotaviruses Revealed Using Large-scale Comparative Genomics.
Journal of virology. 2012 Jun 13;
Group A rotaviruses (RVs) are eleven-segmented, double-stranded RNA viruses and primary causes of gastroenteritis in young children. Despite their medical relevance, the genetic diversity of modern human RVs is poorly understood, and the impact of vaccine use on circulating strains remains unknown. In this study, we report the complete genome sequence analysis of 58 RVs isolated from children with severe diarrhea and/or vomiting at Vanderbilt University Medical Center (VUMC) in Nashville, TN during years spanning community vaccine implementation (2005-2009). The RVs analyzed include 36 G1P, 18 G3P, and 4 G12P Wa-like genogroup 1 strains with VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 genotype constellations of I1-R1-C1-M1-A1-N1-T1-E1-H1. By constructing phylogenetic trees, we identified 2-5 subgenotype alleles for each gene. The results show evidence of intra-genogroup gene reassortment among the co-circulating strains. However, several isolates from different seasons maintained identical allele constellations, consistent with the notion that certain RV clades persisted in the community. By comparing the genes of VUMC RVs to those of other archival and contemporary RV strains for which sequences are available, we defined phylogenetic lineages and verified that the diversity of the strains analyzed in this study reflects that seen in other regions of the world. Importantly, the VP4 and VP7 proteins encoded by VUMC RVs and other contemporary strains show amino acid changes in or near neutralization domains, which might reflect antigenic drift of the virus. Thus, this large-scale, comparative genomics study of modern human RVs provides significant insight into how this pathogen evolves during its spread in the community.