USE OF TRAIL COMPOSITIONS AS ANTIVIRAL AGENTS

摘要

Dengue fever is an important tropical illness for which there is currently no virus-specific treatment. Common gene expression changes, using Affymetrix GeneChips (HG-Ul 33A), were seen using several types of infected primary human cells (human umbilical vein endothelial cells (HUVECs), dendritic cells (DCs), monocytes and B cells). Tissue necrosis factor-related apoptosis inducing ligand (TRAIL), one of the common response genes, may provide additional immune modulator functions present in virus infected cells, and additional interactions between type-I and II IFN response genes and TRAIL that will increase the innate immunity to the virus or even to other pathogens like bacteria.. Dengue virus induces TRAIL expression in immune cells and HUVECs at the mRNA and protein level and was found to be dependent on an intact IFN type I signaling pathway. Anti-TRAIL antibody incubation with primary cells showed an increase in DV accumulation and conversely, a decrease in DV RNA was seen in presence of recombinant TRAIL (i.e., for example, human rTRAIL). These data suggest that TRAIL may play a role in the anti-viral response to DV infection and is a candidate for anti-viral interventions against DV. Further, TRAIL antiviral function does not promote apoptosis. The role of exogenous TRAIL in dendritic cells confirmed a strong anti-inflammatory response due to the lowering of production of mediators of inflammation present in dengue infection.