The rotaviruses are recognized as the major cause of diarrhea in children and animals throughout the world. The long-term research objective of this laboratory is to understand, in detail, the molecular biology and replication strategies of the rotaviruses. Studies of the simian rotavirus SA11, are continuing to elucidate the structure and function of the individual genes and their protein products. The goals of the proposal are; (1) To determine the functions of the rotavirus genome by determining and analyzing the complete nucleotide sequence of the SA11 RNA segments; (2) To map selected antigenic and biologic domains of genome segment 4. Neutralization escape mutants will be produced to map the neutralizing monoclonals that identify the NP1 site on the hemagglutinin (VP4) of SA11. In addition sequencing gene 4 of a SA11 variant (called SA11-4F) with an altered genome segment 4 electrophoretic mobility and unique plaquing and other biologic properties will be performed. (3) To use gene manipulation and expression methods to analyze SA11 gene structure and protein function. We propose to characterize the rotavirus RNA sequences and proteins responsible for RNA transcription, RNA replication and assembly of the RNA segments into particles. In vitro morphogenesis systems will be used to determine the genes and protein interactions critical for particle formation and particle budding through the endoplasmic reticulum membrane, and we will continue efforts to develop methods to rescue rotavirus mRNA to dsRNA in infectious particles. Finally, immunocytochemical studies using new polyclonal antibodies to each rotavirus gene product will be used localize proteins within infected cells during various stages of replication. It is anticipated that these studies will provide fundamental information that will help develop strategies to prevent and control this important disease in children and animals.
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