Evolutionary Dynamics of Human Rotaviruses: Balancing Reassortment with Preferred Genome Constellations

Abstract

Group A human rotaviruses (RVs) are a major cause of severe gastroenteritis in infants and young children. Yet, aside from the genes encoding serotype antigens (VP7; G-type and VP4; P-type), little is known about the genetic make-up of emerging and endemic human RV strains. To gain insight into the diversity and evolution of RVs circulating at a single location over a period of time, we sequenced the eleven-segmented, double-stranded RNA genomes of fifty-one G3P[8] strains collected from 1974 to 1991 at Children's Hospital National Medical Center, Washington, D. C. During this period, G1P[8] strains typically dominated, comprising on average 56% of RV infections each year in hospitalized children. A notable exception was in the 1976 and 1991 winter seasons when the incidence of G1P[8] infections decreased dramatically, a trend that correlated with a significant increase in G3P[8] infections. Our sequence analysis indicates that the 1976 season was characterized by the presence of several genetically distinct, co-circulating clades of G3P[8] viruses, which contained minor but significant differences in their encoded proteins. These 1976 lineages did not readily exchange gene segments with each other, but instead remained stable over the course of the season. In contrast, the 1991 season contained a single major clade, whose genome constellation was similar to one of the 1976 clades. The 1991 clade may have gained a fitness advantage after reassorting with as of yet unidentified RV strain(s). This study reveals for the first time that genetically distinct RV clades of the same G/P-type can co-circulate and cause disease. The findings from this study also suggest that, although gene segment exchange occurs, most reassortant strains are replaced over time by lineages with preferred genome constellations. Elucidation of the selective pressures that favor maintenance of RVs with certain sets of genes may be necessary to anticipate future vaccine needs.

Modeling rotavirus strain dynamics in developed countries to understand the potential impact of vaccination on genotype distributions

“…Evidence argues against such changes occurring. For example, it has been noted that closely related strains can persist over multiple seasons, and that greater genetic diversity can exist among strains belonging to a single G-type circulating in the same year than strains belonging to that same G-type reemerging 12-15 y later (43,54). It seems unlikely that such strains lose then regain some "fitness factor" during the intervening years.…”

Genetic linkage of capsid protein-encoding RNA segments in group A equine rotaviruses

“…dConsensus sequences from equine complete genome sequences. rotaviruses tend to present constellations of genes that remain stable over time (Heiman et al, 2008;Matthijnssens et al, 2012;McDonald et al, 2009). Human RVA can be divided into three major genome constellations (GI-GIII), being the Wa strain as the prototype for GI, DS-1 for GII and AU-1 for GIII.…”

“…Human RVA can be divided into three major genome constellations (GI-GIII), being the Wa strain as the prototype for GI, DS-1 for GII and AU-1 for GIII. This strong association of genes (genome constellations) has been explained by specific interactions of the viral proteins (Benati et al, 2010;Heiman et al, 2008;Iturriza-Gò mara et al, 2003;McDonald et al, 2009). Thus, genes from one specific genome constellation appear to co-segregate, restricting reassortment amongst different genotypes.…”

“…Although each of the 11 gene segments can theoretically segregate independently during strain reassortment, a genetic linkage between VP6, VP7, VP4 and NSP4 has been reported for certain RVA strains (Martella et al, 2010;McDonald et al, 2009;Song & Hao, 2009). Thus, viral protein interactions might drive the selection of strains that can replicate and spread better in different species (Iturriza-Gò mara et al, 2003;Santos et al, 2003).…”

Production and Functional Properties of Dairy Products Containing Lactophorin and Lactadherin

“…Rotavirus has two independent serotypes (G and P types), and they are defined by VP7 and VP4, respectively. Epidemiological studies on rotavirus showed that strains with G-types of G1, G2, G3, and G4 and those with P-types of P[4] and P [8] are the most prevalent causes of rotavirus gastroenteritis in humans (Gentsch et al, 2005;Santos and Hoshino, 2005;McDonald et al, 2009). Furthermore, the rotavirus G/Ptype distribution varies from year-to-year (O'Ryan, 2009).…”