Abstract
Background: Dengue virus (DENV) infection can cause lifethreatening dengue hemorrhage fever and shock syndrome (DHF/DSS). Currently there is no effective treatment to prevent the development of DHF/DSS, except supporting care. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays important roles in the pathogenesis of DHF/DSS. Because autophagy is involved in DENV replication and MIF can induce cell autophagy through thegenerationof reactiveoxygenspecies (ROS), the effect of MIF on DENV replication was studied. Methods: DENV infection of human hepatoma cell line Huh7 cells, with or without the presence of MIF inhibitor, ISO-1 or ROS scavenger N-acetyl-L-cysteine (NAC), was detected by antiNS1 antibody and flow cytometry. In addiiton, MIF knockdown cells were generated by shRNA to compare virus replication and autophagy formation (LC3-II expression) induced by DENV infection. Results: In the presence of ISO-1 as well as NAC, DENV replication in Huh-7 cells was reduced. Diminished MIF expression by shRNA transfection further confirmed DENV replication and autophagy induced byDENVwere reduced inMIF knockdown cells. Conclusion: Taken together, these data suggest that blocking MIF by its inhibitor or antibodymay not only reduce proinflammatory response but also virus replication during DENV infection.
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