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

Antiviral Research
Yen-Chung LaiTrai-Ming Yeh

Abstract

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 DEN...Continue Reading

Citations

Jun 20, 2020·Expert Review of Anti-infective Therapy·Harmanjit SinghPrerna Chauhan
Jul 25, 2018·Journal of Biomedical Science·Hong-Ru ChenTrai-Ming Yeh
Oct 12, 2018·Emerging Microbes & Infections·Naoko Uno, Ted M Ross
Aug 9, 2020·BioMed Research International·Jian SunHiromichi Iwasaki
Nov 3, 2020·Archives of Virology·Jesús A Mosquera-Sulbaran, Hugo Hernández-Fonseca

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