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...

Acute gastrointestinal infections due to rotaviruses and other enteric pathogens are major causes of morbidity and mortality in infants and young children throughout the world. Breastfeeding can reduce the rate of serious gastroenteritis in infants; however, the degrees of protection offered against rotavirus infection vary in different populations. The mechanisms associated with milk-mediated protection against viral gastroenteritis have not been fully elucidated.We have isolated a macromolecular component of human milk that inhibits the replication of rotaviruses in tissue culture and prevents the development of gastroenteritis in an animal model system. Purification of the component indicates that the antiviral activity is associated with an acidic fraction (pI = 4.0-4.6), which is free of detectable immunoglobulins. Furthermore, high levels of antiviral activity are associated with an affinity-purified complex of human milk mucin. Deglycosylation of the mucin complex results in the loss of antiviral activity. Further purification indicated that rotavirus specifically binds to the milk mucin complex as well as to the 46-kD glycoprotein component ofthe complex. Binding to the 46-kD component was substantially reduced after chemical hydrolysis of sialic acid.We have documented that human milk mucin can bind to rotavirus and inhibit viral replication in vitro and in vivo. Variations in milk mucin glycoproteins may be associated with different levels of protection against infection with gastrointestinal pathogens. (J. Clin. Invest. 1992. 90:1984

A series of monoclonal antibodies was isolated which reacted with one of two major surface proteins of rhesus rotavirus. Thirty-six monoclonal antibodies immunoprecipitated the 82-kilodalton outer capsid protein, the product of the fourth gene, the viral hemagglutinin. These monoclonal antibodies exhibited hemagglutination inhibition activity and neutralized rhesus rotavirus to moderate or high titer. Three monoclonal antibodies immunoprecipitated the 38-kilodalton outer capsid glycoprotein, the eighth or ninth gene product. These three monoclonal antibodies neutralized rhesus rotavirus to high titer and also inhibited viral hemagglutination.

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