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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Experimental Virology Study Section (EVR)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
Kavanagh, Owen V; Ajami, Nadim J; Cheng, Elly et al. (2010) Rotavirus enterotoxin NSP4 has mucosal adjuvant properties. Vaccine 28:3106-11
Li, Zongli; Baker, Matthew L; Jiang, Wen et al. (2009) Rotavirus architecture at subnanometer resolution. J Virol 83:1754-66
Greenberg, Harry B; Estes, Mary K (2009) Rotaviruses: from pathogenesis to vaccination. Gastroenterology 136:1939-51
Gilger, Mark A; El-Serag, Hashem B; Gold, Benjamin D et al. (2008) Prevalence of endoscopic findings of erosive esophagitis in children: a population-based study. J Pediatr Gastroenterol Nutr 47:141-6
Berkova, Zuzana; Crawford, Sue E; Blutt, Sarah E et al. (2007) Expression of rotavirus NSP4 alters the actin network organization through the actin remodeling protein cofilin. J Virol 81:3545-53
Berkova, Z; Crawford, S E; Trugnan, G et al. (2006) Rotavirus NSP4 induces a novel vesicular compartment regulated by calcium and associated with viroplasms. J Virol 80:6061-71
El-Serag, Hashem B; Gilger, Mark A; Shub, Mitchell D et al. (2006) The prevalence of suspected Barrett's esophagus in children and adolescents: a multicenter endoscopic study. Gastrointest Endosc 64:671-5
Gilger, Mark A; Gold, Benjamin D (2005) Pediatric endoscopy: new information from the PEDS-CORI project. Curr Gastroenterol Rep 7:234-9