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Suppression of autophagy by mycophenolic acid contributes to inhibition of HCV replication in human hepatoma cells.

Suppression of autophagy by mycophenolic acid contributes to inhibition of HCV replication in human hepatoma cells.
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Fang S, Su J, Liang B, Li X, Li Y, Jiang J, Huang J, Zhou B, Ning C, Li J, Ho W, Li Y, Chen H, Liang H, Ye L,


Fang S, Su J, Liang B, Li X, Li Y, Jiang J, Huang J, Zhou B, Ning C, Li J, Ho W, Li Y, Chen H, Liang H, Ye L, (click to view)

Fang S, Su J, Liang B, Li X, Li Y, Jiang J, Huang J, Zhou B, Ning C, Li J, Ho W, Li Y, Chen H, Liang H, Ye L,

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Scientific reports 2017 03 097() 44039 doi 10.1038/srep44039

Abstract

Previous studies have shown that mycophenolic acid (MPA) has an anti-HCV activity. However, the mechanism of MPA-mediated inhibition of HCV replication remains to be determined. This study investigated whether MPA has an effect on autophagy, a cellular machinery required for HCV replication, thereby, inhibits HCV replication in Huh7 cells. MPA treatment of Huh7 cells could suppress autophagy, evidenced by decreased LC3B-II level and conversion of LC3B-I to LC3B-II, decreased autophagosome formation, and increased p62 level compared to MPA-untreated cells. Tunicamycin treatment or HCV infection could induce cellular autophagy, however, MPA also exhibited its inhibitory effect on tunicamycin- or HCV infection-induced autophagy. The expression of three autophagy-related genes, Atg3, Atg5, and Atg7 were identified to be inhibited by MPA treatment. Over-expression of these genes could partly recover HCV replication inhibited by MPA; however, silencing their expression by siRNAs could enhance the inhibitory effect of MPA on HCV. Collectively, these results reveal that suppression of autophagy by MPA plays a role in its anti-HCV activity. Down-regulating the expression of three autophagy-related genes by MPA involves in its antiviral mechanism.

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