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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK030144-12
Application #
3229302
Study Section
Experimental Virology Study Section (EVR)
Project Start
1981-08-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
12
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
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