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

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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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81173636 to L. S.; and No. 81473401 to W. Z.), and the Natural Science Foundation of Guangdong Province (S2011040005339 to L. S.). We thank Dr. Haiyang He for the provision of rotavirus and technical help. We are also grateful for useful comments on the manuscript by the colleagues of Sino-American Cancer Research Institute, Guangdong Medical College.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Pharmacy, Guangdong Medical College, No. 1, Xincheng Road of Songshan Lake Science and Technology Industry Park, Dongguan, 523808, Guangdong, China

    Haohai Huang, Liping Liang, Lijun Song & Wenchang Zhao

  2. Institution of Traditional Chinese Medicine and New Pharmacy Development, Guangdong Medical College, Dongguan, 523808, Guangdong, China

    Haohai Huang, Liping Liang, Lijun Song & Wenchang Zhao

  3. Sino-American Cancer Research Institute, Guangdong Medical College, Dongguan, 523808, Guangdong, China

    Dan Liao

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  1. Haohai Huang
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Correspondence to Lijun Song or Wenchang Zhao.

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Huang, H., Liao, D., Liang, L. et al. Genistein inhibits rotavirus replication and upregulates AQP4 expression in rotavirus-infected Caco-2 cells. Arch Virol 160, 1421–1433 (2015). https://doi.org/10.1007/s00705-015-2404-4

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