Independent segregation of two antigenic specificities (VP3 and VP7) involved in neutralization of rotavirus infectivity.

Abstract

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...

Antigenic Analysis of Rotavirus Isolates using Monoclonal Antibodies Specific for Human Serotypes 1, 2, 3 and 4, and SA11

“…We have previously considered these isolates to be similar or identical to the St. Thomas 3 strain based on our observations that antiserum to one of them (FH4453) neutralizes the St. Thomas 3 strain. However, this does not eliminate the possibility that they represent naturally occurring intertypic strains as described by Hoshino et al (1985b) and we intend to investigate them further.…”

“…It was not until the successful adaptation of HRV to growth in cell culture (Sato et al, 1981;Urasawa et al, 1981) that an appropriate definition of subgroup and serotype was reported and neutralization assays enabling distinction of individual serotypes were developed (Wyatt et al, 1982;Beards & Flewett, 1984). While gene-coding assignment has previously revealed that the antigenic determinant responsible for subgroup is coded for by gene 6 and that gene 8 or 9, depending on the strain, codes for the serotype-specific determinant Greenberg et al, 1983) more recent information suggests that a further polypeptide, VP3, which is coded by gene 4, may also play a role in serotype specificity (Hoshino et al, 1985b;Offit & Blavat, 1986). The subgroup determinant is located on a 41000 tool.…”

Distinct yearly change of serotype distribution of human rotavirus in Thailand as determined by ELISA and PCR

“…As shown in Rotavirus has two outer capsid proteins, VP7 and VP4, which are independent neutralization antigens [19]. Serotype specificity of rotaviruses is ascribed mainly to the antigenic identity of VP7.…”

Rotavirus Infection: A Perspective on Epidemiology, Genomic Diversity and Vaccine Strategies

“…Group A rotavirus classification based on neutralizing VP7 antigens is termed G-type (since VP7 is a glycoprotein), and VP4 neutralizing antigens is termed P-type (since VP4 is a protease sensitive protein). Genes that encode VP7 and VP4 can segregate separately, resulting in a large amount of antigenic diversity [42,88]. So far, 23 G-types and 32 P-types of rotavirus have been reported (Tables 1, 2) [24,57,94].…”