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J Virol, March 1998, p. 2183-2191, Vol. 72, No. 3
Equipe Hépatite C, CNRS-UMR 319, Institut de Biologie de Lille et Institut Pasteur de Lille, 59021 Lille cédex, France
Received 8 September 1997/Accepted 4 December 1997
The hepatitis C virus (HCV) genome encodes two envelope
glycoproteins (E1 and E2). These glycoproteins interact to form a noncovalent heterodimeric complex which is retained in the endoplasmic reticulum (ER). To identify whether E1 and/or E2 contains an
ER-targeting signal potentially involved in ER retention of the E1-E2
complex, these proteins were expressed alone and their intracellular
localization was studied. Due to misfolding of E1 in the absence of E2,
no conclusion on the localization of its native form could be drawn from the expression of E1 alone. E2 expressed in the absence of E1 was
shown to be retained in the ER similarly to E1-E2 complex. Chimeric
proteins in which E2 domains were exchanged with corresponding domains
of a protein normally transported to the plasma membrane (CD4) were
constructed to identify the sequence responsible for its ER retention.
The transmembrane domain (TMD) of E2 (C-terminal 29 amino acids) was
shown to be sufficient for retention of the ectodomain of CD4 in the ER
compartment. Replacement of the E2 TMD by the anchor signal of CD4 or a
glycosyl phosphatidylinositol (GPI) moiety led to its expression on the
cell surface. In addition, replacement of the E2 TMD by the anchor
signal of CD4 or a GPI moiety abolished the formation of E1-E2
complexes. Together, these results suggest that, besides having a role
as a membrane anchor, the TMD of E2 is involved in both complex
formation and intracellular localization.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
A Retention Signal Necessary and Sufficient for Endoplasmic
Reticulum Localization Maps to the Transmembrane Domain of
Hepatitis C Virus Glycoprotein E2
*
Corresponding author. Mailing address: Equipe
Hépatite C, CNRS-UMR 319, Institut de Biologie de Lille et
Institut Pasteur de Lille, 1 rue Calmette, BP447, 59021 Lille
cédex, France. Phone: (33) 3 20 87 11 60. Fax: (33) 3 20 87 11 11. E-mail: jdubuis{at}infobiogen.fr.
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