Abstract
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.
Highlights
Dengue virus (DV), a mosquito-borne positive sense RNA virus of the Flaviviridae family, is the major cause of dengue in tropical and sub tropical regions [1]
Because both U937 and Peripheral blood mononuclear cells (PBMCs) possess Fc receptors on the cell surface that could lead to increased virus load when presence of dengue virus antibodies at a subneutralizing level, we performed detection of dengue virus antibodies in the human serum using Dengue IgG ELISA kit (Abnova)
These results suggest that certain factors present in human serum are associated with DV particles and able to promote DV infectivity
Summary
Dengue virus (DV), a mosquito-borne positive sense RNA virus of the Flaviviridae family, is the major cause of dengue in tropical and sub tropical regions [1]. Significant decrease in level of HDL was observed in severe DHF/DSS patients compared to patients with milder disease, which cloud be a potential clinical predictor for DHF/ DSS [13]. It has not been investigated if HDL has a similar effect on DV infection as found in the case of HCV infection. We found that DV exhibits increased infectivity in presence of human serum Such an enhancement is mediated by direct association of DV with serum apolipoprotein A-I (ApoA-I), the major protein component in HDL, which facilitates cell entry of DV via cell receptor SR-BI
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