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Abstract
EV71 is a positive-sense single-stranded RNA virus that belongs to the Picornaviridae family. EV71 infection may cause various symptoms ranging from hand-foot-and-mouth disease to neurological pathological conditions such as aseptic meningitis, ataxia, and acute transverse myelitis. There is currently no effective treatment or vaccine available. Various compounds have been examined for their ability to restrict EV71 replication. However, most experiments have been performed in rhabdomyosarcoma or Vero cells. Since the gastrointestinal tract is the entry site for this pathogen, we anticipated that orally ingested agents may exert beneficial effects by decreasing virus replication in intestinal epithelial cells. In this study, curcumin (diferuloylmethane, C21H20O6), an active ingredient of turmeric (Curcuma longa Linn) with anti-cancer properties, was investigated for its anti-enterovirus activity. We demonstrate that curcumin treatment inhibits viral translation and increases host cell viability. Curcumin does not exert its anti-EV71 effects by modulating virus attachment or virus internal ribosome entry site (IRES) activity. Furthermore, curcumin-mediated regulation of mitogen-activated protein kinase (MAPK) signaling pathways is not involved. We found that protein kinase C delta (PKCδ) plays a role in virus translation in EV71-infected intestinal epithelial cells and that curcumin treatment decreases the phosphorylation of this enzyme. In addition, we show evidence that curcumin also limits viral translation in differentiated human intestinal epithelial cells. In summary, our data demonstrate the anti-EV71 properties of curcumin, suggesting that ingestion of this phytochemical may protect against enteroviral infections.
Highlights
EV71 is a positive-sense single-stranded RNA virus of the family Picornaviridae
To examine the susceptibility of gut epithelial cells to EV71 infection, HT29 human intestinal epithelial cells were infected with EV71 at an multiplicity of infection (MOI) of 1 (Fig 1A)
To further examine whether curcumin can affect the binding of EV71 to intestinal epithelial cells, EV71 was treated with curcumin at 4 ̊C for one hour and used to infect cells at the MOI of 1 at 37 ̊C for an additional hour
Summary
Other notable members of this family include poliovirus, coxsackievirus, EV-D68, and rhinovirus These pathogens are known for their highly contagious properties, susceptibility to mutation, and ability to cause serious diseases. For other gut pathogens such as rotavirus and norovirus, compounds that can decrease intestinal viral titers have been shown to exert therapeutic effects in animal experiments [4]. Phytochemical ingestion has proven to be effective in the prevention of cancer [6]. Several clinical trials have been performed to test the effectiveness of curcumin in cancer prevention, with some showing encouraging results [8]. Whether curcumin treatment can exert antiviral activity in intestinal epithelial cells has not been investigated. We examined the anti-EV71 activity and associated mechanisms of curcumin in intestinal epithelial cells. Our results show that the ability of curcumin to modulate PKCδ activation may contribute to its anti-EV71 activity
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