In Vitro and in Vivo Modulation of Rotavirus Infection by Soy Isoflavones

Rotavirus infections are the most common cause of diarrhea in infants worldwide. Although two vaccines have been recently developed and approved, their access to developing countries, where rotavirus incidence is high, may be limited. Therefore, the investigation of other cost effective strategies including nutritional interventions to reduce the incidence or severity of rotavirus infections is still needed. Currently, about 25% of formula-fed infants in the U.S. are fed soy-based infant formulas containing naturally high concentration of isoflavones, which possess anti-viral and antiinflammatory properties. Thus, the objective of this research was to investigate the potential effectiveness and underlying mechanisms whereby dietary isoflavones, at concentrations present in soy-based infant formula, would inhibit rotavirus infectivity in vitro and in vivo. Using kidney monkey epithelial cells (MA-104), a well-established model for rotavirus infections, isoflavones decreased rotavirus infectivity by 33-74% compared to the control across a wide range of rotavirus concentrations in vitro. Genistin was identified as the biologically active isoflavone beginning at 30 muM through the reduction of rotavirus attachment to the host cells. The neonatal piglet model was used to test whether isoflavone could also modulate the severity and duration of rotavirus infections in vivo. As a first step, the temporal gastrointestinal host responses to rotavirus infection were established. Rotavirus infection in the neonatal piglet caused severe diarrhea, villus blunting, and an up-regulation of the adapative immune responses within 2d post-infection, which did not return to baseline by 8d post-infection. In contrast, the acute inflammatory responses, which peaked between 2-6d post-infection, were normalized by 8d post-infection. Using this model, dietary genistin and genistein at concentrations present in soy based infant formulas did not affect the severity or duration of rotavirus infections. The severity of the rotavirus infection as well as the low dose of genistein used in this study may explain the results obtained. To our knowledge this is the first study demonstrating and characterizing the anti-RV properties of isoflavones in vitro. Future studies are warranted to test the effect of isoflavones on rotavirus infectivity in the neonatal piglet using milder doses of rotavirus and higher doses of genistein.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Nutritional Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Andres, Aline

Contributors dc:contributor

• Donovan, Sharon M.

• Health Sciences, Nutrition

Language dc:language

eng

Identifier

(MiAaPQ)AAI3290165

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84952