Dengue virus entry into liver (HepG2) cells is independent of hsp90 and hsp70.

Recently, several stress-related proteins including GRP78, hsp70, and hsp90 have been implicated as dengue virus receptors in various cell types, with hsp90/70 being implicated as a receptor complex in monocytes and macrophages, while GRP78 has been implicated as a liver cell expressed dengue virus receptor. To assess whether the hsp90/70 complex plays a role in the internalization of the dengue viruses into liver cells, we undertook infection inhibition studies with lipopolysaccharide and antibodies directed against both hsp70 and hsp90, individually and in combination. No inhibition of any dengue serotype was seen in the presence of lipopolysaccharide or antibodies directed against either hsp70 or hsp90 either singly or in combination. A moderate inhibition of dengue virus serotype 2 entry into liver cells was observed in the presence of antibodies directed against GRP78. These results confirm a proposed role for GRP78 as a dengue virus serotype 2 receptor protein and suggest that the recently identified hsp90/70 complex does not play a role in dengue virus internalization into liver cells. (c) 2007 Wiley-Liss, Inc.