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Journal of Virology, July 2005, p. 8400-8409, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.8400-8409.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Role of N-Linked Glycans in the Functions of Hepatitis C Virus Envelope Glycoproteins

Anne Goffard,1,2 Nathalie Callens,1 Birke Bartosch,3 Czeslaw Wychowski,1 François-Loïc Cosset,3 Claire Montpellier,1 and Jean Dubuisson1*

CNRS-UPR2511, Institut de Biologie de Lille, Institut Pasteur de Lille, Lille, France,1 Service de Virologie/UPRES EA3610, Faculté de Médecine, Université-Lille 2, Lille, France,2 Laboratoire de Vectorologie Rétrovirale et Thérapie Génique, INSERM U412, IFR74, Ecole Normale Supérieure de Lyon, Lyon, France3

Received 29 November 2004/ Accepted 13 March 2005

Hepatitis C virus (HCV) encodes two viral envelope glycoproteins. E1 contains 4 or 5 N-linked glycosylation sites and E2 contains up to 11, with most of the sites being well conserved, suggesting that they play an essential role in some functions of these proteins. For this study, we used retroviral pseudotyped particles harboring mutated HCV envelope glycoproteins to study these glycans. The mutants were named with an N followed by a number related to the relative position of the potential glycosylation site in each glycoprotein (E1N1 to E1N4 for E1 mutants and E2N1 to E2N11 for E2 mutants). The characterization of these mutants allowed us to define three phenotypes. For the first group (E1N3, E2N3, E2N5, E2N6, E2N7, and E2N9), the infectivities of the mutants were close to that of the wild type. The second group (E1N1, E1N2, E1N4, E2N1, and E2N11) contained mutants that were still infectious but whose infectivities were reduced to <50% that of the wild type. The third group (E2N2, E2N4, E2N8, and E2N10) contained mutants that had almost totally lost infectivity. The absence of infectivity of the E2N8 and E2N10 mutants was due to the lack of incorporation of the E1E2 heterodimer into HCVpp, which was due to misfolding of the heterodimer, as shown by immunoprecipitation with conformation-sensitive antibodies and by a CD81 pull-down assay. The absence of infectivity of the E2N2 and E2N4 mutants indicated that these two glycans are involved in controlling HCV entry. Altogether, the data indicate that some glycans of HCV envelope glycoproteins play a major role in protein folding and others play a role in HCV entry.

* Corresponding author. Mailing address: Unité Hépatite C, CNRS-UPR2511, Institut de Biologie de Lille, 1 rue Calmette, BP447, 59021 Lille, France. Phone: (33) 3 20 87 11 60. Fax: (33) 3 20 87 12 01. E-mail: jean.dubuisson{at}ibl.fr.

Journal of Virology, July 2005, p. 8400-8409, Vol. 79, No. 13
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.13.8400-8409.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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