Human rotaviruses are the leading cause of severe infantile diarrhea in the world. In the immunocompromised or elderly adult, rotaviruses are also an important cause of diarrheal disease. Rotavirus infection may also be associated with exacerbations of illness in patients with inflammatory bowel disease. In addition, rotaviruses can cause gastroenteritis in many other mammalian and avian species. In the decade since the discovery of human rotavirus much information has been gained concerning the nature of the viral genome (double stranded segmented RNA), the protein structure of the virus, the serologic and genetic relationship among rotaviral strains, and the epidemiology and pathophysiology of human rotavirus infection. Little information, however, has been generated concerning the genetic basis of viral virulence or host range. Furthermore, the protective role, in vivo, of antibody (IgG vs. IgA) to the two separate rotavirus surface proteins has not been examined. The genetic basis of virulence and the molecular determinants of host protection have obvious relevance to development of a successful strategy for the prevention of rotavirus diarrhea. The genetic basis of rotavirus virulence and host range will be determined by evaluating the pathogenicity of selected murine rotavirus X bovin rotavirus and murine rotavirus X simian rotavirus reassortants in a murine rotavirus infection model. As a second approach to determine the basis of viral virulence, alterations in viral pathogenicity will be examined in murine rotavirus variants selected with neutralizing monoclonal antibodies directed at either of the two viral surface proteins. Determinants of host protection will be studied with monoclonal antibodies (IgG and IgA) directed at the two surface proteins of murine rotavirus. Passive transfer of these monoclonal antibodies will be used to determine the rotavirus protein(s) and specific domains of the protein(s) that stimulate protective immunity. Comparison of the biologic effect of monoclonal antibodies with similar specificities but different isotypes (IgG vs. IgA) should help to clarify the role of local immunity in protection. The antigenic domains protective role of immunization with synthetic peptides.
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