

@article {3806,
	title = {Cyclosporin a inhibits rotavirus replication and restores interferon-beta signaling pathway in vitro and in vivo.},
	journal = {\{\{\}PloS\{\}\} one},
	volume = {8},
	number = {8},
	year = {2013},
	pages = {e71815},
	abstract = {Rotavirus \{\{\}(RV)\{\}\} is the most common cause of severe diarrhea among infants and young children. Currently, there is no specific drug available against rotavirus, largely due to the lack of an ideal target molecule which has hampered drug development. Our previous studies have revealed that cyclosporin A \{\{\}(CsA)\{\}\} might be potentially useful as an \{\{\}anti-RV\{\}\} drug. We therefore used both cellular and mouse models to study the immunological safety and effectiveness of \{\{\}CsA\{\}\} as an \{\{\}anti-RV\{\}\} drug. We found that \{\{\}CsA\{\}\} treatment of \{\{\}HT-29\{\}\} cells before, during, and after viral infection efficiently inhibited Wa strain \{\{\}RV\{\}\} replication and restored \{\{\.I}FN-\{\&\}\{\#\}x3B2;\{\}\} expression in a \{\{\}HT-29\{\}\} cell line model. Exploring the underlying mechanisms showed that \{\{\}CsA\{\}\} promoted Interferon Regulatory Factor-5 \{\{\}(IRF-5)\{\}\} expression (a key positive regulator of the type I \{\{\.I}FN\{\}\} signaling pathway), but not \{\{\.I}RF-1,\{\}\} \{\{\.I}RF-3,\{\}\} or \{\{\.I}RF-7.\{\}\} Additionally, \{\{\}CsA\{\}\} inhibited \{\{\}SOCS-1\{\}\} expression (the key negative regulator of \{\{\.I}FN-\{\&\}\{\#\}x3B1;/\{\&\}\{\#\}x3B2;),\{\}\} but not \{\{\}SOCS-2\{\}\} or \{\{\}SOCS-3.\{\}\} The antiviral effect of \{\{\}CsA\{\}\} was confirmed in an \{\{\}RV-infected\{\}\} neonatal mouse model by evaluation of antigen clearance and assessment of changes in intestinal tissue pathology. Also, no differences in T cell frequency or proliferation between the \{\{\}CsA-\{\}\} and vehicle-treated groups were observed. Thus, both our in vitro and in vivo findings suggest that \{\{\}CsA,\{\}\} through modulating the expression of key regulators in \{\{\.I}FN\{\}\} signaling pathway, promote type I \{\{\.I}FN-based\{\}\} intracellular innate immunity in \{\{\}RV\{\}\} host cells. These findings suggest that \{\{\}CsA\{\}\} may be a useful candidate to develop a new \{\{\}anti-RV\{\}\} strategy, although further evaluation and characterization of \{\{\}CsA\{\}\} on \{\{\}RV-induced\{\}\} diarrhea are warranted.},
	doi = {10.1371/journal.pone.0071815},
	url = {http://dx.doi.org/10.1371/journal.pone.0071815},
	author = {Shen, Zigang and He, Haiyang and Wu, Yuzhang and Li, Jintao}
}
