Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding, and neutralization

Emilia Falkowska, Francis Kajumo, Edie Garcia, John F. Reinus, Tatjana Dragic

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) is a major human pathogen that causes serious liver disease, including cirrhosis and hepatocellular carcinoma. The primary target cells of HCV are hepatocytes, and entry is restricted by interactions of the envelope glycoproteins, E1 and E2, with cellular receptors. E1 and E2 form noncovalently linked heterodimers and are heavily glycosylated. Glycans contribute to protein folding and transport as well as protein function. In addition, glycans associated with viral envelopes mask important functional domains from the immune system and attenuate viral immunogenicity. Here, we explored the role of N- and O-linked glycans on E2, which is the receptor binding subunit of the HCV envelope. We identified a number of glycans that are critical for viral entry. Importantly, we showed that the removal of several glycans significantly increased the inhibition of entry by sera from HCV-positive individuals. Only some of the glycans that aifected entry and neutralization were also important for CD81 binding. Our results show that HCV envelope-associated glycans play a crucial role in masking functionally important regions of E2 and suggest a new strategy for eliciting highly neutralizing antibodies against this virus.

Original languageEnglish (US)
Pages (from-to)8072-8079
Number of pages8
JournalJournal of Virology
Volume81
Issue number15
DOIs
StatePublished - Aug 2007

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Hepatitis C virus
neutralization
Polysaccharides
glycoproteins
polysaccharides
Hepacivirus
Virus Internalization
receptors
protein folding
protein transport
Protein Folding
transport proteins
liver diseases
Protein Transport
hepatoma
Masks
Hepatitis C virus glycoprotein E2
Neutralizing Antibodies
neutralizing antibodies
hepatocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding, and neutralization. / Falkowska, Emilia; Kajumo, Francis; Garcia, Edie; Reinus, John F.; Dragic, Tatjana.

In: Journal of Virology, Vol. 81, No. 15, 08.2007, p. 8072-8079.

Research output: Contribution to journalArticle

Falkowska, Emilia ; Kajumo, Francis ; Garcia, Edie ; Reinus, John F. ; Dragic, Tatjana. / Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding, and neutralization. In: Journal of Virology. 2007 ; Vol. 81, No. 15. pp. 8072-8079.
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