Macrophage migration inhibitory factor enhances dengue virus replication through autophagy formation and ROS generation (168.10)

Abstract

Abstract Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine which has been identified as a risk factor in dengue virus (DENV) infection. Previous study showed MIF deficient mice exhibit lower virus titer than wild type mice during DENV infection. However, the mechanism is still unknown. Herein, we first examined whether MIF interfere DENV replication in vitro. By using flow cytometry assay, we found both MIF inhibitor ISO-1 or MIF knock down could reduce DENV replication in Huh 7 cells. Moreover, we found that reactive oxygen species (ROS) of Huh 7 cells induced by DENV infection were also decreased in the presence of ISO-1. ROS is an inducer of autophagy which has been showed to be involved in DENV replication. Thus, we hypothesize MIF facilitate DENV replication through ROS generation and autophagy formation. We found ISO-1, MIF knock down, or ROS scavenger N-acetyl-L-cysteine (NAC) could reduce autophagy during DENV infection by western blotting analysis. The LC3 punctae formation was also reduced in MIF knock down Huh 7 cells during DENV infection. Taken together, blocking of MIF by its inhibitor or antibody may not only prevent inflammation but also viral replication during DENV infection.