Rotaviruses were discovered in the 1960s in animals. The virus was first described in humans when it was found by electron microscopy in duodenal biopsies from children with acute gastroenteritis (9
Rotaviruses are 70-nm icosahedral viruses that belong to the family Reoviridae. Seven rotavirus serogroups (serogroups A to G) are described. Most human pathogens belong to groups A, B, and C. Group A rotaviruses are the most important from a public health standpoint.
The virus is composed of three protein shells, an outer capsid, an inner capsid, and an internal core, that surround the 11 segments of double-stranded RNA (Fig. ). For the most part, each gene segment codes for a single protein. When mixed infection with more than one rotavirus strain occurs, the gene segments from the parental viruses may reassort independently, producing reassortants of mixed parentage, a source of viral diversity.
FIG. 2. Schematic representation of a rotavirus virion. The virus is composed of three protein shells, an outer capsid, an inner capsid, and an internal core, that surround the 11 segments of double-stranded RNA. The outer capsid proteins VP4 and VP7 are neutralization (more ...)
Four major structural and nonstructural proteins are of interest in vaccine development: VP6, NSP4, VP7, and VP4. VP6, the most abundant viral structural protein, is found in the inner capsid (43
). VP6 bears group-specific antigenic determinants. NSP4 is a nonstructural protein and has been shown to be an enterotoxin (2
VP7 and VP4 are structural proteins found in the outer capsid. These two proteins define the serotype of the virus and are considered to be critical for vaccine development because they are targets for neutralizing antibodies that may provide both serotype-specific and, in some instances, cross-reactive protection (38
). The VP7 protein is glycosylated, and serotypes determined by this protein are termed G serotypes. Fourteen G serotypes have been identified.
VP4 is a protease-cleaved protein, and serotypes determined by this protein are termed P serotypes. P types have been difficult to characterize by traditional methods of virus neutralization; therefore, molecular methods have been used to define a genotype based on sequence analysis. These genotypes correlate well with known serotypes, so the genotypes are tentatively designated in brackets (e.g., P1A). Strains are generally designated by their G serotype specificities (e.g., serotypes G1 to G4 and G9).
Human rotaviruses exhibit enormous diversity. The gene segments that encode the G and P proteins can segregate independently, giving rise to strains with at least 42 different P-G serotype combinations (33
). However, a small number of rotavirus strains bearing VP7 G serotypes G1 to G4 and G9 and VP4 P genotypes P1B, P2A, and P1A are predominant worldwide. In a recent study, four G types (G1, G2, G3, and G4) in conjunction with P1A or P1B represented over 88% of the strains analyzed worldwide. Serotype G9 viruses associated with P1A or P2A have been emerging since the late 1990s and now represent approximately 4% of global isolates (Fig. ) (74
FIG. 3. Distribution of rotavirus serotypes worldwide and in the United States. (A) Global distribution from 1989 to 2004. The G serotypes of >88% of rotavirus strains worldwide are G1, G2, G3, and G4. The P serotype of >80% of (more ...)
G and P serotype distributions differ geographically. P1AG1 is the globally predominant strain, representing over 70% of rotavirus infections in North America (Fig. ), Europe, and Australia but only about 30% of the infections in South America and Asia and 23% of those in Africa (74
). G9 strains now constitute the predominant strains in some parts of Asia and Africa, and G8 strains are proportionally more frequently isolated in Africa. In South America, G5 strains have emerged in children with diarrhea, and G9 is associated with more severe disease in Latin America (53
). Similarly, the distribution of the VP4 P2A antigen differs according to region. P2A strains now constitute over 50% of the strains circulating in Africa, whereas P1A is associated with most rotavirus strains from the rest of the world (76
Implementation of an effective rotavirus vaccine program will need to take into account the geographical variation of prevalent strains. The continued identification of the most common G and P serotypes for inclusion in vaccines is an important priority. After the introduction of a vaccine candidate, monitoring of circulating strains may be necessary, as vaccine pressure may lead to the selection of novel rotavirus strains.