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Journal of Virology, January 2000, p. 702-709, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Functional Characterization of Intracellular and Secreted Forms of a Truncated Hepatitis C Virus E2 Glycoproteindagger

Mike Flint,1 Jean Dubuisson,2 Catherine Maidens,1 Richard Harrop,3 Geoffrey R. Guile,3 Persephone Borrow,3 and Jane A. McKeating1,*

School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ,1 and The Edward Jenner Institute for Vaccine Research, Compton, Newbury RG20 7NN,3 United Kingdom, and Equipe Hepatite C, CNRS-UMR 8526, Institut de Biologie de Lille et Institut Pasteur de Lille, 59021 Lille Cedex, France2

Received 6 July 1999/Accepted 19 October 1999

The E2 protein of hepatitis C virus (HCV) is believed to be a virion surface glycoprotein that is a candidate for inclusion in an antiviral vaccine. A truncated soluble version of E2 has recently been shown to interact with CD81, suggesting that this protein may be a component of the receptor for HCV. When expressed in eukaryotic cells, a significant proportion of E2 forms misfolded aggregates. To analyze the specificity of interaction between E2 and CD81, the aggregated and monomeric forms of a truncated E2 glycoprotein (E2661) were separated by high-pressure liquid chromatography and analyzed for CD81 binding. Nonaggregated forms of E2 preferentially bound CD81 and a number of conformation-dependent monoclonal antibodies (MAbs). Furthermore, intracellular forms of E2661 were found to bind CD81 with greater affinity than the extracellular forms. Intracellular and secreted forms of E2661 were also found to differ in reactivity with MAbs and human sera, consistent with differences in antigenicity. Together, these data indicate that proper folding of E2 is important for its interaction with CD81 and that modifications of glycans can modulate this interaction. Identification of the biologically active forms of E2 will assist in the future design of vaccines to protect against HCV infection.

* Corresponding author. Present address: Pfizer Ltd., Central Research, Sandwich, Kent CT13 9NJ, United Kingdom. Phone: (44) 1304 616 161. Fax: (44) 1304 658 480. E-mail: jane_mckeating{at}sandwich.pfizer.com.

dagger Publication no. 10 from the Edward Jenner Institute for Vaccine Research.

Journal of Virology, January 2000, p. 702-709, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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