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The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus
Abstract:
The liver is one of the main target organs of Marburg virus (MBG), a filovirus causing severe haemorrhagic fever with a high fatality rate in humans and non-human primates. MBG grown in certain cells does not contain neuraminic acid, but has terminal galactose on its surface glycoprotein. This observation indicated that the asialoglycoprotein receptor (ASGP-R) of hepatocytes may serve as a receptor for MBG in the liver. Binding studies revealed that the attachment of MBG to ASGP-R-expressing 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 cells to MBG infection 4.5-fold. Interaction of MBG with the hepatic ASGP-R could thus explain the marked hepatotropism of the virus.
Insights
Marburg virus (MBG) targets the liver. Researchers found that MBG uses the asialoglycoprotein receptor (ASGP-R) on liver cells, explaining its strong attraction to the liver.
Area of Science:
- Virology
- Hepatology
- Molecular Biology
Background:
- Marburg virus (MBG) is a filovirus causing severe hemorrhagic fever.
- The liver is a primary target organ for MBG infection.
- MBG possesses terminal galactose on its surface glycoprotein.
Purpose of the Study:
- To investigate the mechanism of MBG hepatotropism.
- To identify the cellular receptor for MBG in liver cells.
Main Methods:
- Binding studies using MBG and ASGP-R-expressing HepG2 cells.
- Inhibition assays with asialofetuin and anti-ASGP-R antiserum.
- MBG infection assays in cells with altered ASGP-R expression.
Main Results:
- MBG attachment to HepG2 cells exhibited ASGP-R ligand-binding characteristics.
- Calcium dependency and inhibition by asialofetuin/antiserum confirmed ASGP-R interaction.
- ASGP-R expression enhanced NIH 3T3 cell susceptibility to MBG infection.
Conclusions:
- The hepatic asialoglycoprotein receptor (ASGP-R) mediates Marburg virus entry into liver cells.
- This interaction explains the pronounced hepatotropism observed in MBG infections.
- Targeting the ASGP-R pathway may offer therapeutic strategies against MBG.