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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.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Lai YC,Chuang YC,Chang CP,Lin YS,Perng GC,Wu HC,Hsieh SL,Yeh TM

doi

10.1016/j.antiviral.2018.05.002

subject

Has Abstract

pub_date

2018-07-01 00:00:00

pages

28-38

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(18)30076-7

journal_volume

155

pub_type

杂志文章

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