Identification of GRP 78 (BiP) as a liver cell expressed receptor element for dengue virus serotype 2

This study sought to identify receptor elements for dengue virus serotype 2 on human liver cells (HepG2) using the viral overlay protein binding assay (VOPBA) technique and Mass Spectrometry fingerprinting. A single major and several minor virus binding bands were observed, and mass spectrometry identified a candidate binding protein for the major binding band as GRP 78 (BiP). GRP78 expression on the cell surface was confirmed, and antibodies directed against both the N and C-terminus of GRP 78 (BiP) altered both the binding of the virus to the cell surface as well as the infectivity profile of HepG2 cells in response to dengue serotype 2 infection. GRP 78 (BiP), which has previously been identified as a co-receptor protein for coxsackievirus A9, is the first non-Fc receptor protein identified for the dengue virus, although GRP78 probably functions as part of a receptor complex.