Diseases caused by dengue virus (DV)
infection vary in severity, with symptoms ranging from mild
fever to life threatening
dengue hemorrhage fever (DHF) and
dengue shock syndrome (DSS). Clinical studies have shown that significant decrease in the level of
lipoproteins is correlated with severe illness in DHF/DSS patients. Available evidence also indicates that
lipoproteins including
high-density lipoprotein (HDL) and
low-density lipoprotein (
LDL) are able to facilitate cell entry of HCV or other flaviviruses via corresponding
lipoprotein receptors. In this study, we found that pre-incubation of DV with human serum leads to an enhanced DV infectivity in various types of cells. Such enhancement could be due to interactions between serum components and DV particles. Through co-immunoprecipitation we revealed that
apolipoprotein A-I (
ApoA-I), the major
protein component in HDL, is associated with DV particles and is able to promote DV
infection. Based on that observation, we further found that
siRNA knockdown of the
scavenger receptor class B type I (SR-BI), the cell receptor of
ApoA-I, abolished the activity of
ApoA-I in enhancement of DV
infection. This suggests that
ApoA-I bridges DV particles and cell
receptor SR-BI and facilitates entry of DV into cells. FACS analysis of cell surface
dengue antigen after virus absorption further confirmed that
ApoA-I enhances DV
infection via promoting initial attachment of the virus to cells. These findings illustrate a novel entry route of DV into cells, which may provide insights into the functional importance of
lipoproteins in
dengue pathogenesis.