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Journal of Virology, April 1999, p. 2641-2649, Vol. 73, No. 4
CNRS-UMR319,
Received 8 September 1998/Accepted 16 December 1998
Hepatitis C virus (HCV) glycoproteins E1 and E2 assemble to form a
noncovalent heterodimer which, in the cell, accumulates in the
endoplasmic reticulum (ER). Contrary to what is observed for proteins
with a KDEL or a KKXX ER-targeting signal, the ER localization of the
HCV glycoprotein complex is due to a static retention in this
compartment rather than to its retrieval from the cis-Golgi region. A
static retention in the ER is also observed when E2 is expressed in the
absence of E1 or for a chimeric protein containing the ectodomain of
CD4 in fusion with the transmembrane domain (TMD) of E2. Although they
do not exclude the presence of an intracellular localization signal in
E1, these data do suggest that the TMD of E2 is an ER retention signal
for HCV glycoprotein complex. In this study chimeric proteins
containing the ectodomain of CD4 or CD8 fused to the C-terminal
hydrophobic sequence of E1 were shown to be localized in the ER,
indicating that the TMD of E1 is also a signal for ER localization. In
addition, these chimeric proteins were not processed by Golgi enzymes,
indicating that the TMD of E1 is responsible for true retention in the
ER, without recycling through the Golgi apparatus. Together, these data
suggest that at least two signals (TMDs of E1 and E2) are involved in
ER retention of the HCV glycoprotein complex.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
The Transmembrane Domain of Hepatitis C Virus
Glycoprotein E1 Is a Signal for Static Retention in the
Endoplasmic Reticulum
*
Corresponding author. Mailing address: Equipe
Hépatite C, CNRS-UMR 319, Institut de Biologie de Lille & Institut Pasteur de Lille, 1 rue Calmette, BP447, 59021 Lille Cedex,
France. Phone: (33) 3-20-87-11-60. Fax: (33) 3-20-87-11-11. E-mail:
jdubuis{at}infobiogen.fr.
Journal of Virology, April 1999, p. 2641-2649, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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