A safe and effective rotavirus vaccine is urgently needed, particularly in developing countries. Critical to vaccine development and implementation is a knowledge base concerning the epidemiology of rotavirus G and P serotypes/genotypes throughout the world. The temporal and geographical distribution of human rotavirus G and P types was reviewed by analysing a total of 45571 strains collected globally from 124 studies reported from 52 countries on five continents published between 1989 and 2004. Four common G types (G1, G2, G3 and G4) in conjunction with P[8] or P[4] represented over 88% of the strains analysed worldwide. In addition, serotype G9 viruses associated with P[8] or P[6] were shown to have emerged as the fourth globally important G type with the relative frequency of 4.1%. When the global G and/or P type distributions were divided into five continents/subcontinents, several characteristic features emerged. For example, the P[8]G1 represented over 70% of rotavirus infections in North America, Europe and Australia, but only about 30% of the infections in South America and Asia, and 23% in Africa. In addition, in Africa (i) the relative frequency of G8 was as high as that of the globally common G3 or G4, (ii) P[6] represented almost one-third of all P types identified and (iii) 27% of the infections were associated with rotavirus strains bearing unusual combinations such as P[6]G8 or P[4]G8. Furthermore, in South America, uncommon G5 virus appeared to increase its epidemiological importance among children with diarrhea. Such findings have (i) confirmed the importance of continued active rotavirus strain surveillance in a variety of geographical settings and (ii) provided important considerations for the development and implementation of an effective rotavirus vaccine (e.g. a geographical P-G type adjustment in the formulation of next generation multivalent vaccines).

A total of 16 different strains of rotavirus derived from seven mammalian species (four each from human and porcine species, two each from equine and simian species, and one each from canine and bovine species) and two avian species (one each from turkeys and chickens) were examined in plaque-reduction neutralization tests. Seven antigenically distinct serotypes were established on the basis of a greater than or equal to 20-fold difference between titers of homologous and heterologous reciprocal neutralizing antibodies. Serotypes 1 (strain Wa) and 2 (strain DS-1) were recovered only from humans. Serotype 3 included human rotavirus strain WALK 57/14, rhesus monkey rotavirus strain MMU18006 , vervet monkey rotavirus strain SA-11, dog rotavirus strain CU-1, and horse rotavirus strain H-2. The newly established serotype 4 was identified in both humans (strain St. Thomas no. 4) and pigs (strains Gottfried , SB-1A, and SB-2). Porcine (strain OSU ) and equine (strain H-1) rotaviruses made up a possible fifth serotype. Bovine rotavirus (strain NCDV) constituted a sixth serotype, and chicken rotavirus (strain Ch 2), which had a prime-strain relation with turkey rotavirus (strain Ty 1), was designated serotype 7. A surprising observation that emerged from this study was the existence of a rotavirus (porcine strain SB-1A) bridging serotypes 4 and 5.

Antiserum prepared against the M37 strain of rotavirus, recovered from an asymptomatic newborn infant in Venezuela, neutralized two prototype human rotaviruses that define two separate serotypes: serotype 1 (Wa) and serotype 4 (ST3). Thus, the M37 strain is a naturally occurring intertypic rotavirus. Analysis of reassortant viruses produced during coinfection in vitro indicated that the observed dual serotype specificity of M37 resulted from sharing a related outer (1-3).The genome of rotaviruses consists of 11 discrete segments (genes) of double-stranded (ds) RNA. These genes reassort with high efficiency during coinfection, and this property has facilitated the selection of reassortant viruses with a mixed constellation of genes derived from two biologically and antigenically distinct rotaviruses. Analysis of reassortant viruses has provided much of our current understanding of gene-product relationships. For example, the fourth gene segment has been shown to code for the outer capsid hemagglutinin protein VP3 (4), which is also the site for protease activation of infectivity (4) and for host-range restriction of rotavirus infectivity (5, 6). The major subgroup antigen(s) was shown to be coded for by the sixth RNA genome segment (7,8). The eighth or ninth genome segment, depending on the virus strain, was shown to code for a major neutralization antigen, VP7 (6,7,9).Hybridoma technology has also aided the functional and structural analysis of the relatively complex rotaviruses. For example, some monoclonal antibodies directed against the fourth rotaviral gene product, VP3, exhibit both hemagglutination-inhibiting and neutralizing activity (8-10). Also, subgroup-specific monoclonal antibodies react with the sixth gene product, VP6 (11), whereas certain monoclonal antibodies directed against the eighth or ninth rotaviral gene product, VP7, exhibit a high level of neutralizing activity (9, 10, 12, 13). Until now the outer capsid VP7 protein has been considered the major neutralization antigen. The recent observation that some monoclonal antibodies directed against VP3 exhibit a moderate to high level of neutralizing activity was not surprising, however, because this antigen is also located on the outer capsid (9, 10, 13).During the course of analyzing rotavirus isolates by the plaque-reduction neutralization (PRN) technique, we observed that hyperimmune guinea pig antiserum raised against the Venezuelan neonatal rotavirus isolate M37 neutralized both serotype 1 (strain Wa) and serotype 4 (strain St. Thomas no. 3) rotaviruses to the same degree (14). A combined genetic and serologic analysis of this "intertypic bridging" phenomenon indicated that the VP3 and VP7 outer capsid proteins of the M37 rotavirus each played a role in the observed dual serotype of the neonatal rotavirus isolate. This indicated that these neutralization specificities present on VP3 and VP7 segregate independently in nature.MATERIALS AND METHODS Viruses. The following cultivatable rotaviruses were used in this study: human rotaviru...