Minocycline suppresses dengue virus replication by down-regulation of macrophage migration inhibitory factor-induced autophagy

Yen Chung Lai, Yung Chun Chuang, Chih Peng Chang, Yee Shin Lin, Guey Chuen Perng, Han Chung Wu, Shie Liang Hsieh, Trai Ming Yeh

研究成果: Article

5 引文 斯高帕斯(Scopus)

摘要

Dengue virus (DENV) infection is the most prevalent mosquito-borne viral infection of which there is no licensed therapeutic drug available. Previous studies have shown that minocycline, an antibiotic, can inhibit DENV infection in vitro. However, the mechanism is not fully understood. It is known that macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is involved in dengue disease development; MIF can induce autophagy, and autophagy can facilitate DENV replication. Therefore, we tested the hypothesis that MIF-induced autophagy is involved in minocycline treatment against DENV infection. We first showed that DENV infection induced MIF secretion and autophagy flux in HuH-7 cells. Suppression of endogenous MIF by short hairpin RNA (shRNA) and inhibition of MIF by its inhibitors attenuated DENV replication and autophagy formation. In addition, minocycline treatment suppressed DENV-induced MIF secretion and autophagy in vitro. Finally, we demonstrated that minocycline treatment attenuated viral load, MIF secretion, autophagy and increase survival in DENV-infected mice. These results suggest that inhibition of MIF-induced autophagy by minocycline might represent an alternative therapeutic approach against DENV infection.

原文English
頁(從 - 到)28-38
頁數11
期刊Antiviral Research
155
DOIs
出版狀態Published - 2018 七月

    指紋

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

引用此