Genistein inhibits rotavirus replication and upregulates AQP4 expression in rotavirus-infected Caco-2 cells

Genistein inhibits rotavirus replication and upregulates AQP4 expression in rotavirus-infected... Rotavirus (RV) is the primary cause of severe dehydrating gastroenteritis and acute diarrheal disease in infants and young children. Previous studies have revealed that genistein can inhibit the infectivity of enveloped or nonenveloped viruses. Although the biological properties of genistein are well studied, the mechanisms of action underlying their anti-rotavirus properties have not been fully elucidated. Here, we report that genistein significantly inhibits RV-Wa replication in vitro by repressing viral RNA transcripts, and possibly viral protein synthesis. Interestingly, we also found that aquaporin 4 (AQP4) mRNA and protein expression, which was downregulated in RV-infected Caco-2 cells, can be upregulated by genistein in a time- and dose-dependent manner. Further experiments confirmed that genistein triggers CREB phosphorylation through PKA activation and subsequently promotes AQP4 gene transcription. These findings suggest that the pathophysiological mechanism of RV infection involves decreased expression of AQP4 and that genistein may be a useful candidate for developing a new anti-RV strategy by inhibiting rotavirus replication and upregulating AQP4 expression via the cAMP/PKA/CREB signaling pathway. Further studies on the effect of genistein on RV-induced diarrhea are warranted. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Genistein inhibits rotavirus replication and upregulates AQP4 expression in rotavirus-infected Caco-2 cells

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Publisher
Springer Journals
Copyright
Copyright © 2015 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-015-2404-4
Publisher site
See Article on Publisher Site

Abstract

Rotavirus (RV) is the primary cause of severe dehydrating gastroenteritis and acute diarrheal disease in infants and young children. Previous studies have revealed that genistein can inhibit the infectivity of enveloped or nonenveloped viruses. Although the biological properties of genistein are well studied, the mechanisms of action underlying their anti-rotavirus properties have not been fully elucidated. Here, we report that genistein significantly inhibits RV-Wa replication in vitro by repressing viral RNA transcripts, and possibly viral protein synthesis. Interestingly, we also found that aquaporin 4 (AQP4) mRNA and protein expression, which was downregulated in RV-infected Caco-2 cells, can be upregulated by genistein in a time- and dose-dependent manner. Further experiments confirmed that genistein triggers CREB phosphorylation through PKA activation and subsequently promotes AQP4 gene transcription. These findings suggest that the pathophysiological mechanism of RV infection involves decreased expression of AQP4 and that genistein may be a useful candidate for developing a new anti-RV strategy by inhibiting rotavirus replication and upregulating AQP4 expression via the cAMP/PKA/CREB signaling pathway. Further studies on the effect of genistein on RV-induced diarrhea are warranted.

Journal

Archives of VirologySpringer Journals

Published: Jun 1, 2015

References

  • Emerging themes in rotavirus cell entry, genome organization, transcription and replication
    Jayaram, H; Estes, MK; Prasad, BV
  • Electrolyte transport in the mammalian colon: mechanisms and implications for disease
    Kunzelmann, K; Mall, M
  • Aquaporins contribute to diarrhoea caused by attaching and effacing bacterial pathogens
    Guttman, JA; Samji, FN; Li, Y; Deng, W; Lin, A; Finlay, BB
  • Solute transporters and aquaporins are impaired in celiac disease
    Laforenza, U; Miceli, E; Gastaldi, G; Scaffino, MF; Ventura, U; Fontana, JM; Orsenigo, MN; Corazza, GR
  • Soy isoflavones and virus infections
    Andres, A; Donovan, SM; Kuhlenschmidt, MS

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