Suppression of dengue virus propagation by sterol carrier protein 2 inhibitor in Aedes Aag2 cell

Dengue fever (DF) and dengue hemorrhagic fever (DHF) resurged during the past decades, which infect approximately 100 million people every year. Currently, there is no effective vaccine or specific treatment for DF or DHF. Dengue virus (DENV), a positive-stranded RNA virus that belongs to Flaviviridae family, is transmitted by mosquito species, mainly Aedes aegypti and Aedes albopictus. It is known that cholesterol plays an important role in the life cycle of DENV in host cells. In Aedes, sterol carrier protein-2 (SCP-2) is critical for cellular cholesterol homeostasis. In this study, we indentified SCP-2 as a critical host factor for DENV propagation in mosquito Aag-2 cell. SCP-2 specific inhibitor treatment drastically hampered the virus entry and replication in cultured cell. The role of SCP-2 in DENV propagation was also confirmed by over-expression and/or expression knock-down study. Furthermore, we showed that the intracellular cholesterol distribution was altered by SCPI-1 treatment, implicating its mode of action. Our results suggested SCP-2 is critical for mosquito vector competence and is a novel target for disease control.