TY - JOUR
T1 - Minocycline suppresses dengue virus replication by down-regulation of macrophage migration inhibitory factor-induced autophagy
AU - Lai, Yen Chung
AU - Chuang, Yung Chun
AU - Chang, Chih Peng
AU - Lin, Yee Shin
AU - Perng, Guey Chuen
AU - Wu, Han Chung
AU - Hsieh, Shie Liang
AU - Yeh, Trai Ming
N1 - Funding Information:
This study was supported by the Grants from the Ministry of Science and Technology Taiwan (MOST 106-2321-B-006-011) and the National Health Research Institutes (NHRI B106-W013). In addition, we thank the technical services provided by the Bio-image Core Facility of the National Core Facility Program for Biotechnology, Ministry of Science and Technology, Taiwan.
Funding Information:
This study was supported by the Grants from the Ministry of Science and Technology Taiwan (MOST 106-2321-B-006-011 ) and the National Health Research Institutes ( NHRI B106-W013 ). In addition, we thank the technical services provided by the Bio-image Core Facility of the National Core Facility Program for Biotechnology, Ministry of Science and Technology, Taiwan. Appendix A
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/7
Y1 - 2018/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.antiviral.2018.05.002
DO - 10.1016/j.antiviral.2018.05.002
M3 - Article
C2 - 29752950
AN - SCOPUS:85046778034
SN - 0166-3542
VL - 155
SP - 28
EP - 38
JO - Antiviral Research
JF - Antiviral Research
ER -
