P034 Inhibition of macrophage migration inhibitory factor reduces dengue virus replication

Abstract

Introduction Dengue virus (DENV) infection can cause life-threatening 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 (1). Because autophagy, which can be induced by reactive oxygen species (ROS), is involved in DENV replication (2), the effect of MIF and ROS on DENV replication in human hepatoma cell line Huh-7 cells was studied. Methods MIF inhibitor, ISO-1 as well as ROS scavenger N-acetyl-L-cysteine (NAC) were applied in DENV-infected Huh-7 cells. In addition, MIF knockdown Huh-7 cells were generated by shRNA transfection to further confirm MIF is involved in DENV infection-induced autophagy. DENV replication was determined by secreted alkaline phosphatase (SEAP) assay as well as flow cytometry. Results We demonstrated that, 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 by DENV were reduced in MIF knockdown cells. Conclusion Taken together, these data suggest that therapeutically blocking MIF by its inhibitor or antibody may not only reduce proinflammatory response but also virus replication during DENV infection. References (1) Assuncao-Miranda I, Amaral FA, et al. Contribution of macrophage migration inhibitory factor to the pathogenesis of dengue virus infection. FASEB J 2010;24(1):218–28. (2) Lee YR, Lei HY, et al. Autophagic machinery activated by dengue virus enhances virus replication. Virology 2008;374(2):240–8.