BioProject

Dengue virus (DENV) is a flavivirus transmitted by mosquitoes, and is the most prevalent arboviral pathogen in the world. More...

Dengue virus (DENV) is a flavivirus transmitted by mosquitoes, and is the most prevalent arboviral pathogen in the world. The extent of acute DENV hepatitis has been linked to severe outcomes such as vascular leakage and hemorrhage, although the means by which hepatic responses to infection contribute to virus replication and disease are not well understood. We conducted an integrated transcriptomic, proteomic, and phosphoproteomic survey of hepatic cellular responses to DENV infection to identify host processes associated with increased inflammation, reduced coagulation factor synthesis, regulation of cell cycle progression and apoptosis, and translational control. Integration of these data sets into a comprehensive network model revealed modulation of several critical host signaling pathways, including PI3K/Akt, Ras/Raf/MAPK, Hsp90, and mTOR signaling. Experimental testing of these pathways demonstrated that Hsp90 inhibition impairs DENV replication, suggesting that heat shock responses may contribute significantly to hepatic infection. Overall design: Huh7 human hepatoma cells were mock-infected or infected with dengue virus 2/New Guinea C strain (MOI=10) and total RNA was extracted from cells collected at 24 and 48h post-infection Less...