Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection.

Abstract

The hepatitis E virus (HEV), a nonenveloped RNA virus, is the causative agent of hepatitis E. The mode by which HEV attaches to and enters into target cells for productive infection remains unidentified. Open reading frame 2 (ORF2) of HEV encodes its major capsid protein, pORF2, which is likely to have the determinants for virus attachment and entry. Using an approximately 56-kDa recombinant pORF2 that can self-assemble as virus-like particles, we demonstrated that cell surface heparan sulfate proteoglycans (HSPGs), specifically syndecans, play a crucial role in the binding of pORF2 to Huh-7 liver cells. Removal of cell surface heparan sulfate by enzymatic (heparinase) or chemical (sodium chlorate) treatment of cells or competition with heparin, heparan sulfate, and their oversulfated derivatives caused a marked reduction in pORF2 binding to the cells. Syndecan-1 is the most abundant proteoglycan present on these cells and, hence, plays a key role in pORF2 binding. Specificity is likely to be dictated by well-defined sulfation patterns on syndecans. We show that pORF2 binds syndecans predominantly via 6-O sulfation, indicating that binding is not entirely due to random electrostatic interactions. Using an in vitro infection system, we also showed a marked reduction in HEV infection of heparinase-treated cells. Our results indicate that, analogous to some enveloped viruses, a nonenveloped virus like HEV may have also evolved to use HSPGs as cellular attachment receptors.

• Authors: Manjula Kalia, Vivek Chandra, Sheikh Abdul Rahman, Deepak Sehgal, Shahid Jameel
• Journal: Journal of virology (J Virol) Vol. 83 Issue 24 Pg. 12714-24 (Dec 2009) ISSN: 1098-5514 [Electronic] United States
• PMID: 19812150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heparan Sulfate Proteoglycans
• ORF2 protein, Hepatitis E virus
• Syndecans
• Viral Proteins

Topics

• Cell Line, Tumor
• Heparan Sulfate Proteoglycans (physiology)
• Hepatitis E virus (physiology)
• Humans
• Syndecans (metabolism)
• Viral Proteins (metabolism)
• Virion (physiology)