Graduation Semester and Year

2010

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Quantitative Biology

Department

Biology

First Advisor

Michael Roner

Abstract

Reovirus and rotavirus are both members of the Reoviridae family and commonly occur in children. Rotavirus induced diarrhea is one of the leading causes of death in children under the age of five worldwide. Identifying new treatment options for an unnecessarily deadly diarrheal infection caused by rotavirus would benefit hundreds of thousands of children a year. Currently, only oral rehydration therapy or costly vaccinations are available to treat or prevent rotavirus diarrhea. Even with their prevalence, little is known about how these two viruses (reovirus and rotavirus) interact when co-infecting cells. Determining these interactions could lead to new treatment options for rotavirus infections. Using the three known human reovirus serotypes (MRV-1LA, MRV-2JO, and MRV-3DE) in vitro co-infections were performed with Rhesus rotavirus (RRV) in MA104 cells. These infections revealed that infectious RRV particle production was greatly inhibited by the presence of MRV-1LA and MRV-2JO, but not affected by the presence of MRV-3DE. To determine which reovirus genes were responsible for the inhibition, co-infections using RRV and two sets of mammalian orthoreovirus monoreassortants (MRV-1LA with MRV-3DE genes and MRV-3DE with MRV-2JO genes) were performed in MA-104 cells. It was determined that when the S2 and S3 genes of MRV-1LA and MRV-2JO were present in the co-infections, infectious particle production was completely inhibited. Next, in vivo studies were performed using Balb/c mice to determine if co-infections with RRV and MRV-1LA, MRV-2JO, or MRV-3DE resulted in lessened diarrhea in comparison to mice singularly infected with RRV. It was found that mice simultaneously co-infected with RRV and MRV-1LA developed diarrhea to a lesser degree than mice singularly infected with RRV. These results indicate that MRV-1LA has the ability to inhibit rotavirus diarrhea in mammals when co-infection occurs. This inhibitory property of MRV-1LA could lead to potential treatment options of rotavirus infections and help many children every year.

Disciplines

Biology | Life Sciences

Comments

Degree granted by The University of Texas at Arlington

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