Ka Ian Tam

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

Rotavirus is the leading cause of severe diarrhea disease in newborns and young children worldwide, estimated to be responsible for over 500,000 adolescent deaths mostly in developing countries each year. Rotavirus-related deaths represent approximately 5% of all deaths in children younger than five years of age worldwide. Previous research has shown that Quillaja saponins demonstrate strong antiviral activity against 7 different viruses, including rotavirus, in vitro. Quillaja saponins, a natural, aqueous extract of triterpenoid saponins obtained from Quillaja saponaria, the Chilean Soap Bark tree that display strong adjuvant activity when used in vaccines. In this study, Quillaja saponins are stable in water and are approved by the US FDA for use as food additives. The proposed mechanism of Quillaja saponins is most likely through binding to membrane sterol of the epithelium of the host's small intestine and prevents rotavirus attachment. I proposed that the addition of Quillaja saponins to water supplies can inhibit rotavirus infection and thereby prevent diarrhea caused by rotavirus. This study evaluated the effect of Quillaja saponin against rotavirus induced diarrhea using mouse rhesus rotavirus diarrhea model. Rhesus rotavirus was orally inoculated into newborn mice for 5 days. Toxicity testing showed that the LD50 of Quillaja saponins is 0.65mg/ml for consecutive 5 days of treatment. Different titers of rotvirus were used to test for antiviral activity, ED50 is at 0.22mg/ml over 5 consecutive days of virus challenge at 500 PFUs. Fractionation of the whole Quillaja saponin through FPLC showed difference in cytotoxicity and antiviral activity among fractions.

Disciplines

Biology | Life Sciences

Comments

Degree granted by The University of Texas at Arlington

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