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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 DENV infection.

Original languageEnglish
Pages (from-to)28-38
Number of pages11
JournalAntiviral Research
Volume155
DOIs
Publication statusPublished - 2018 Jul

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Macrophage Migration-Inhibitory Factors
Dengue Virus
Minocycline
Autophagy
Virus Replication
Down-Regulation
Virus Diseases
Dengue
Culicidae
Viral Load
Small Interfering RNA
Cytokines
Anti-Bacterial Agents

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

Cite this

@article{297537f491f44848a148bacf757cbbdd,
title = "Minocycline suppresses dengue virus replication by down-regulation of macrophage migration inhibitory factor-induced autophagy",
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 DENV infection.",
author = "Lai, {Yen Chung} and Chuang, {Yung Chun} and Chang, {Chih Peng} and Lin, {Yee Shin} and Perng, {Guey Chuen} and Wu, {Han Chung} and Hsieh, {Shie Liang} and Yeh, {Trai Ming}",
year = "2018",
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Minocycline suppresses dengue virus replication by down-regulation of macrophage migration inhibitory factor-induced autophagy. / Lai, Yen Chung; Chuang, Yung Chun; Chang, Chih Peng; Lin, Yee Shin; Perng, Guey Chuen; Wu, Han Chung; Hsieh, Shie Liang; Yeh, Trai Ming.

In: Antiviral Research, Vol. 155, 07.2018, p. 28-38.

Research output: Contribution to journalArticle

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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

PY - 2018/7

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