Rotavirus diversity and evolution in the post-vaccine world

Abstract

Rotaviruses (RVs) are a large genetically diverse population of segmented double-stranded (ds) RNA viruses that are important causes of gastroenteritis in many animal species. The human RVs are responsible for the deaths of nearly 450,000 infants and young children each year, most occurring in developing countries. Recent large-scale sequencing efforts have revealed that the genomes of human RVs typically consist of phylogenetically linked constellations of eleven dsRNA segments. The presence of such preferred constellations indicate that the human RV genes have co-evolved to produce protein sets that work optimally together to support virus replication. Two of the viral genes encode virion outer capsid proteins (VP7 and VP4) whose antigenic properties define the G/P type of the virus. From year-to-year and place-to-place, the G/P type of human RVs associated with disease can fluctuate dramatically, phenomena that can be associated with the presence and behavior of genetically distinct RV clades. The recent introduction of two live attenuated RV vaccines [RotaTeq (TM) and Rotarix (TM)] into the childhood vaccination programs of various countries has been highly effective in reducing the incidence of RV diarrheal disease. Whether the widespread use of these vaccines will introduce selective pressures on human RVs, triggering genetic and antigenic changes that undermine the effectiveness of vaccinations programs, is uncertain and will require continued surveillance of human RVs.

Figure 1

Rotavirus capsid structure and dsRNA genome. (A) Intact triple-layered virion with VP4 spikes projecting from the VP7 outer capsid shell. (B) Cut-away of virion revealing the three protein layers of the virion: VP2, VP6, and VP7. Note that the foot of the VP4 spike extends into the VP6 layer. (C) A VP6 hexamer, VP7 hexamer, and embedded VP4 spike, with the VP8* and VP5* regions of VP4 identified. (D) Double-stranded RNA segments of the RV genome resolved by gel electrophoresis. Segments are labeled as g1-g11 (g = gene), and their protein products are listed. Associated functions or properties of the protein products are given (Genotype name). The underlined letter identifies the segment in the gene constellation acronym: Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx.

Figure 2

G/P-genotypes of RVs recovered from children with gastroenteritis at Vanderbilt University Medical Center during three winter-spring seasons. Sample number (n).

Figure 3

Distribution of RV Genotypes Reported to the WHO Surveillance Network in 2010. Sample number (n).