Coexpression of hepatitis C virus envelope proteins E1 and E2 in cis improves the stability of membrane insertion of E2.
The hepatitis C virus (HCV) genome encodes two envelope glycoproteins, E1 and E2. These proteins contain a large N-terminal ectodomain, and are anchored into membranes by their C-terminal transmembrane domain (TMD). The TMDs of HCV envelope proteins are multifunctional. In addition to their role as membrane anchors, they possess a signal sequence function in their C-terminal half, and play a major role in subcellular localization and assembly of these envelope proteins. In this work, the expression of full-length E2 led to secretion of a proportion of this protein, which is likely to be due to inefficient membrane insertion of a fraction of E2 expressed alone. However, when E1 and E2 were coexpressed from the same polyprotein, E2 was not secreted and remained tightly associated with membranes, suggesting that an early interaction between the TMDs of HCV envelope proteins improves the stability of membrane insertion of E2. These results reinforce the hypothesis that the TMDs of E1 and E2 are major factors in the assembly of the HCV envelope glycoprotein complex.
Cocquerel
Laurence
L
CNRS-FRE2369, Equipe Hépatite C, IBL/Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP447, 59021 Lille Cedex, France1.
Meunier
Jean-Christophe
JC
CNRS-FRE2369, Equipe Hépatite C, IBL/Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP447, 59021 Lille Cedex, France1.
Op de Beeck
Anne
A
CNRS-FRE2369, Equipe Hépatite C, IBL/Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP447, 59021 Lille Cedex, France1.
Bonte
Dorine
D
CNRS-FRE2369, Equipe Hépatite C, IBL/Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP447, 59021 Lille Cedex, France1.
Wychowski
Czeslaw
C
CNRS-FRE2369, Equipe Hépatite C, IBL/Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP447, 59021 Lille Cedex, France1.
Dubuisson
Jean
J
CNRS-FRE2369, Equipe Hépatite C, IBL/Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP447, 59021 Lille Cedex, France1.
D002462:Cell Membrane / Q000821:virology; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D006023:Glycoproteins / Q000378:metabolism*; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D017510:Protein Folding; D013237:Stereoisomerism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D019065:Virus Assembly
C087035:E1 protein, Hepatitis C virus; D006023:Glycoproteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus