THE ASIALOGLYCOPROTEIN RECEPTOR IS A POTENTIAL LIVER-SPECIFIC RECEPTOR FOR MARBURG VIRUS

The liver is one of the main target organs of Marburg virus (MBG), a f ilovirus causing severe haemorrhagic fever with a high fatality rate i n humans and non-human primates. MBG grown in certain cells does not c ontain neuraminic acid, but has terminal galactose on its surface glyc oprotein. This observation indicated that the asialoglycoprotein recep tor (ASGP-R) of hepatocytes may serve as a receptor for MBG in the liv er. Binding studies revealed that the attachment of MBG to ASGP-R-expr essing HepG2 cells, but not to ASGP-R-negative E6 Vero cells, has the characteristics of ligand binding to the ASGP-R: binding is dependent on calcium and is inhibited by excess asialofetuin and by anti-ASGP-R antiserum. Asialofetuin and the specific antiserum also inhibited MBG infection of HepG2 cells. In addition, it was shown that expression of ASGP-R cDNA in NIH 3T3 cells enhanced the susceptibility of these cel ls to MBG infection 4.5-fold. Interaction of MBG with the hepatic ASGP -R could thus explain the marked hepatotropism of the virus.