STRUCTURAL AND FUNCTIONAL CHARACTERIZATION OF A PUPAL CUTICLE PROTEIN FROM AEDES AEGYPTI IMPLICATED IN DENGUE VIRAL INFECTION

Abstract

Previously, the virulence of DENV incubated with Pupal cuticle protein from Aedes aegypti (AaPC) was reduced in the mice model, but the underlaying mechanism remains unknown. Here, we report that AaPC is an intrinsically disordered protein and its residues Asp59, Asp61, Glu71, Asp73, Ser75 and Asp80 interact with the domain I/II of DENV envelope protein. AaPC shows its inhibitory effects to DENV infection by directly interacting with human immune receptors DC-SIGN and CD4. Moreover, our studies suggest that AaPC is also involved in the immune response of human dermal fibroblast (HDF) cells during Dengue infection by using transcriptome analysis, which shows that AaPC treated HDF cells are differentially expressing of genes in chemokine receptor binding, interferon-beta production and MHC protein complex. Our studies enhance our understanding of the role of AaPC in mitigating viral infection and suggest AaPC as a potential target for developing inhibitors or antibodies to control against Dengue virus.