Previous Article | Next Article 
Journal of Virology, July 2000, p. 6217-6222, Vol. 74, No. 13
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Coreceptor-Dependent Inhibition of the Cell Fusion
Activity of Simian Immunodeficiency Virus Env Proteins
Chinglai
Yang,
Qingyuan
Yang, and
Richard W.
Compans*
Department of Microbiology and Immunology,
Emory University School of Medicine, Atlanta, Georgia 30322
Received 5 November 1999/Accepted 10 April 2000
 |
ABSTRACT |
The cytoplasmic tail (R peptide) sequence is able to regulate the
fusion activity of the murine leukemia virus (MuLV) envelope (Env)
protein. We have previously shown that this sequence exerts a profound
inhibitory effect on the fusion activity of simian immunodeficiency
virus (SIV)-MuLV chimeric Env proteins which contain the extracellular
and transmembrane domains of the SIV Env protein. Recent studies have
shown that SIV can utilize several alternative cellular coreceptors for
its fusion and entry into the cell. We have investigated the fusion
activity of SIV and SIV-MuLV chimeric Env proteins using cells that
express different coreceptors. HeLa cells were transfected with plasmid
constructs that carry the SIV or SIV-MuLV chimeric Env protein genes
and were overlaid with either CEMx174 cells or Ghost Gpr15 cells, which
express the Gpr15 coreceptor for SIV, or Ghost CCR5 cells, which
express CCR5, an alternate coreceptor for SIV. The R-peptide sequence
in the SIV-MuLV chimeric proteins was found to inhibit the fusion with
CEMx174 cells or Ghost Gpr15 cells. However, a significant level of
fusion was still observed when HeLa cells expressing the chimeric Env
proteins were cocultivated with Ghost CCR5 cells. These results show
that the R-peptide sequence exerts differential effects on the fusion
activity of SIV Env proteins using target cells that express
alternative coreceptors.
| |
TEXT |
The envelope (Env) proteins of
retroviruses play an important role in virus infection and replication,
as they mediate virus entry into the cells through interacting with
virus receptors and then induce fusion between viral and cellular
membranes. Retrovirus Env proteins are type I transmembrane proteins.
They are synthesized as precursor proteins which are subsequently
processed into two subunits, the surface protein (SU) and the
transmembrane protein (TM), by a cellular protease (21, 24,
40). The Env proteins of human immunodeficiency virus (HIV) and
simian immunodeficiency virus (SIV) are unusual in that they contain
very long cytoplasmic domains (with more than 150 amino acids) in
comparison with most other viral Env proteins, which contain
cytoplasmic domains with less than 50 amino acids. It has been reported
that mutations in the cytoplasmic domain of the HIV and SIV Env
proteins affect their incorporation into virus particles and their
membrane fusion activities (19, 45). For SIV, it has been
shown that passage in human T-cell lines, such as CEMx174 cells,
results in the truncation of its long cytoplasmic domain to 18 amino
acids, and such a truncation of the cytoplasmic domain increases the
membrane fusion activity of the SIV Env protein and enhances SIV
replication in these cell lines (7, 23, 35, 45). However,
due to an unknown mechanism, the full-length Env protein of SIV confers
an advantage for virus replication in rhesus peripheral blood
mononuclear cells (23, 26). Previous studies have shown that
the truncation of the SIVmac239 Env protein cytoplasmic
domain results in a conformational change in its extracellular domain
(38). However, the mechanism by which the cytoplasmic domain
affects the replication of SIV is still not clearly understood.
Regulation of the fusion activity of viral Env proteins by changes in
the cytoplasmic domain has also been observed with other viruses. In
murine leukemia virus (MuLV), the processing of the Env protein removes
a C-terminal fragment of 16 amino acids, which has been designated the
R peptide (20, 22). It has been shown that removal of the R
peptide is important for activating the protein's membrane fusion
activity (32, 33). Cells expressing the truncated MuLV Env
protein, but not the full-length form, induce extensive syncytium
formation when they are cocultivated with cells expressing receptors
for MuLV. Similar observations have also been reported for the Env
protein of type D retroviruses (3, 37). The regulation of
the membrane fusion activity of the Env proteins by its processing in
virions may be an advantage for the virus, since it may prevent the
cytopathic effect of the Env protein that otherwise might be
detrimental to virus production. We have shown that the MuLV R peptide
also exerts a profound inhibitory effect on cell fusion activity of
SIV-MuLV chimeric Env proteins, in which the cytoplasmic domain of the
SIV Env protein is replaced by that of the MuLV Env protein
(42).
In recent studies, it has been found that in addition to CD4, membrane
fusion induced by HIV and SIV Env proteins requires the presence of
specific coreceptors, which are seven-transmembrane proteins also
serving as receptors for chemokines (1, 10, 13, 14, 17). It
has been shown that the SIV Env protein can utilize CCR5, Gpr1 (Bonzo),
and Gpr15 (BOB) as coreceptors (2, 4, 9, 11, 15, 29, 36).
The discovery of the coreceptors for the HIV and SIV Env proteins has
shed new light on the mechanism of their membrane fusion activities.
Several studies have reported that soluble CD4 enhances the interaction of the HIV and SIV Env proteins with their coreceptors (28, 30). Furthermore, it has been shown that interaction of the SU
protein with CD4 results in a conformational change in the HIV Env
protein (25, 27, 41). By analogy with influenza virus
hemagglutinin (HA), it was postulated that the interaction with CD4
induces a conformational change in the ectodomain of the HIV and SIV
Env proteins which enhances their interaction with coreceptors and, in
turn, results in the extension of the fusion peptide at the N terminus
of the TM protein to insert it into the target membrane to initiate the
fusion process (12, 31).
In this study, to further investigate the mechanism of fusion
inhibition by the MuLV R peptide, we examined the cell fusion activities of SIV-MuLV chimeric Env proteins in relation to their coreceptor usage. We also constructed HIV-MuLV chimeric Env proteins and compared their abilities to induce cell fusion. Shown in Fig. 1A is a schematic diagram of the chimeric
Env proteins used for this study. As shown in Fig. 1B and C, the
expression levels of the chimeric proteins were comparable
with each other as well as with those of their wild-type Env
protein counterparts. Surface expression and secretion of gp120
by each chimeric Env protein were also found to be similar to
those of their wild-type counterparts. Therefore, the
replacement of the HIV or SIV Env protein cytoplasmic domain with the
cytoplasmic domain of the MuLV Env protein does not significantly
affect the expression or transport of the chimeric proteins.
View larger version (30K):
[in this window]
[in a new window]
|
FIG. 1.
(A) Schematic diagram of the transmembrane region of Env
protein constructs used in this study. Black boxes represent the
transmembrane domains of the SIV or HIV Env protein, hatched boxes
represent cytoplasmic sequences of MuLV origin, gray boxes represent
the MuLV R-peptide sequence, and white boxes represent the SU or
cytoplasmic domain sequences of SIV or HIV origin (the SU and
full-length cytoplasmic domains of SIV and HIV Env proteins are not
drawn to scale). Construction of genes encoding the chimeric Env
proteins was carried out by following standard cloning procedures
described previously (42). (B) Expression of SIV and
SIV-MuLV chimeric Env proteins. Lanes 1, mock transfection; lanes 2, full-length SIV Env; lanes 3, S-Menv; lanes 4, S-MenvR-; lanes 5, SIVenv733T+R; lanes 6, SIVenv733T. (C) Expression of HIV and HIV-MuLV
chimeric Env proteins. Lanes 1, mock transfection; lanes 2, full-length
HIV Env; lanes 3, H-Menv; lanes 4, H-MenvR-. Proteins were expressed in
HeLa cells using the vaccinia virus T7 expression system
(18). Surface biotinylation and immunoprecipitation were
carried out as described previously (42).
|
|
Fusion activity of SIV-MuLV chimeric Env proteins in the
presence of coreceptor CCR5.
It has been reported that
SIVmac239, which we used for construction of SIV-MuLV
chimeric proteins, can use CCR5 as its coreceptor (9, 29).
We therefore tested the cell fusion activity of SIV-MuLV chimeric Env
proteins in Ghost cells expressing CD4 and CCR5 (Ghost CCR5 cells,
Ghost Gpr15 cells, and Ghost CXCR4 cells were obtained from the
National Institutes of Health [NIH] AIDS Research and Reference
Reagent Program, and Ghost [3] parental cells were
obtained from Vineet N. KewalRamani and Dan R. Littman). To our
surprise, as shown in Fig. 2, all
SIV-MuLV chimeric Env proteins, with or without the MuLV R peptide,
induced extensive cell fusion in Ghost CCR5 cells, at a level similar
to that induced by the wild-type SIV Env protein. In contrast, when we
tested the same constructs in CEMx174 cells, the results reconfirmed our previous finding that the presence of the MuLV R peptide greatly inhibited the fusion activity of the SIV-MuLV chimeric Env proteins in
these cells (data not shown) (42). Since the same cells
(HeLa) were used for Env protein expression in both experiments, the possibility of differences in expression of chimeric proteins can be
excluded. These results indicated that the presence of the MuLV
R-peptide sequence in the cytoplasmic domain of the SIV-MuLV chimeric
Env proteins does not inhibit their cell fusion activity in the
presence of the coreceptor CCR5, indicating that there are factors in
CEMx174 cells important for the fusion inhibition activity of the MuLV
R peptide. It should be noted that CEMx174 cells and the Ghost CCR5
cells are of different origin and that CEMx174 cells are suspension
cells, while the Ghost CCR5 cells are attached cells which form a
monolayer in culture.
View larger version (141K):
[in this window]
[in a new window]
|
FIG. 2.
Fusion activity of SIV and SIV-MuLV chimeric Env
proteins in cells expressing the coreceptor CCR5. Env proteins were
expressed in HeLa cells using the vaccinia virus T7 expression system.
HeLa cells were infected by recombinant virus VTF7-3 (a recombinant
vaccinia virus expressing the T7 polymerase, provided by B. Moss) for
1 h and then transfected with DNA constructs encoding the Env
proteins. At 12 h posttransfection, HeLa cells were overlaid with
Ghost cells (obtained from the NIH AIDS Research and Reference Reagent
Program) which express CD4 and CCR5. Cell fusion pictures were taken at
8 h after overlay of Ghost CCR5 cells under a Nikon microscope.
(a) Mock transfection; (b) full-length SIV Env; (c) S-Menv; (d)
S-MenvR-; (e) SIVenv733T+R; (f) SIVenv733T.
|
|
Fusion activity of SIV-MuLV chimeric Env proteins in the presence
of coreceptor Gpr15.
It was discovered that CEMx174 cells do not
express the coreceptor CCR5. Rather, they express an orphan chemokine
receptor, Gpr15, which can serve as the coreceptor for SIV infection
(11, 15, 36). We therefore obtained Ghost cells which
express CD4 and Gpr15 and used them for the study of the cell fusion
activities of the SIV-MuLV chimeric Env proteins. As shown in Fig.
3, both the full-length and truncated
(SIVenv733T) SIV Env proteins induced extensive cell fusion, while the
control, in which HeLa cells were transfected with vector plasmid, did
not show any cell fusion (compare Fig. 3b and f with a). Regarding the
SIV-MuLV chimeric Env proteins, S-Menv did not induce observable
syncytium formation above the control level (Fig. 3c), while S-MenvR-,
in which the R peptide in the MuLV cytoplasmic domain of the chimeric
protein is truncated, induced syncytium formation at a level similar to that induced by the SIV Env proteins (Fig. 3d). Moreover, SIVenv733T+R, in which the MuLV R-peptide sequence is attached to the C terminus of
SIVenv733T, also did not induce any significant level of cell fusion
(Fig. 3e). The difference in cell fusion activities was not the result
of the differences in the length of the cytoplasmic domain, based on
our results in previous studies showing that extensive cell fusion was
induced by a truncated SIV Env protein with a 33-amino-acid cytoplasmic
domain, similar in length to that of the MuLV Env protein
(42). These results are in agreement with our observation
that the presence of the MuLV R peptide in the cytoplasmic domain of
the SIV-MuLV chimeric Env proteins can profoundly inhibit their cell
fusion activity in CEMx174 cells. Therefore, we conclude from these
results that the fusion activity of the SIV-MuLV chimeric Env proteins
is inhibited by the MuLV R peptide when Gpr15 is used as the
coreceptor, but not when CCR5 is used as the coreceptor in the same
cell type.
View larger version (140K):
[in this window]
[in a new window]
|
FIG. 3.
Fusion activity of SIV and SIV-MuLV chimeric Env
proteins in cells expressing the coreceptor Gpr15. Env proteins were
expressed in HeLa cells using the vaccinia virus T7 expression system.
HeLa cells were infected by recombinant virus VTF7-3 for 1 h and
then transfected with DNA constructs encoding the Env proteins. At
12 h posttransfection, HeLa cells were overlaid with Ghost cells
(obtained from the NIH AIDS Research and Reference Reagent Program)
which express CD4 and Gpr15. Cell fusion pictures were taken at 8 h after overlay of Ghost Gpr15 cells under a Nikon microscope. (a) Mock
transfection; (b) SIVenv; (c) S-Menv; (d) S-MenvR-; (e) SIVenv733T+R;
(f) SIVenv733T.
|
|
Fusion activity of HIV-MuLV chimeric Env proteins.
We have
shown that the presence of the MuLV R peptide can profoundly affect the
cell fusion activity of the SIV-MuLV chimeric Env proteins with cells
expressing the coreceptor Gpr15, such as Ghost Gpr15 and CEMx174 cells.
To further understand the mechanism of fusion inhibition by the MuLV R
peptide, we also studied its effect on the cell fusion activity of
HIV-MuLV chimeric Env proteins in comparison with that of the wild-type
HIV Env protein. The HIV Env protein backbone we used to generate
HIV-MuLV chimeric Env proteins is from HIV-IIIB, which utilizes CXCR4
as a coreceptor (17). We expressed the HIV-MuLV chimeric Env
proteins in HeLa cells and then overlaid them with HeLa T4 cells. As
shown in Fig. 4, the HIV-MuLV chimeric
Env proteins induced extensive cell fusion, similar to that observed
with the wild-type HIV Env protein. We also tested the fusion activity
of the HIV-MuLV chimeric Env proteins with Ghost CXCR4 cells, and a
similar result was observed (data not shown). These results indicate
that unlike SIV-MuLV chimeric Env proteins, the presence of the MuLV R
peptide in the HIV-MuLV chimeric Env protein does not suppress its cell
fusion activity.
View larger version (180K):
[in this window]
[in a new window]
|
FIG. 4.
Fusion activity of HIV and HIV-MuLV chimeric Env
proteins. Env proteins were expressed in HeLa cells using the vaccinia
virus T7 expression system. HeLa cells were infected by recombinant
virus VTF7-3 for 1 h and then transfected with DNA constructs
encoding the Env proteins. At 12 h posttransfection, HeLa cells
were overlaid with HeLa T4 cells (obtained from the NIH AIDS Research
and Reference Reagents Program) which express CD4 and fusin. Cell
fusion pictures were taken at 8 h after overlay of HeLa cells
under a Nikon microscope. (a) Mock transfection; (b) full-length HIV
Env; (c) H-Menv; (d) H-MenvR-.
|
|
We have investigated the cell fusion activities of the SIV-MuLV and
HIV-MuLV chimeric Env proteins in relation to their coreceptor
usage.
Our results show that the presence of the MuLV R peptide
in the
cytoplasmic domain of the HIV-MuLV chimeric proteins does
not affect
their cell fusion activity. More interestingly, we
found that the R
peptide in the SIV-MuLV chimeric Env proteins
showed no fusion
inhibition activity with Ghost cells which express
CD4 and the
coreceptor CCR5. However, when Ghost cells which express
CD4 and the
coreceptor Gpr15 were used for fusion studies, the
fusion activity of R
peptide-containing constructs was greatly
reduced in comparison with
that of the wild-type SIV Env protein
or other chimeric proteins which
lacked the R peptide. Our results
thus demonstrate that the inhibitory
effect of the MuLV R peptide
on cell fusion activities of the SIV Env
proteins depends on the
coreceptor expressed by the target cells. The
observed differences
in fusion inhibition activity of the MuLV R
peptide also indicate
that the SIV Env protein may utilize different
domains to interact
with alternate coreceptor molecules and that the
presence of the
R peptide may selectively affect one of these domains.
We also
observed that the chimeric Env protein S-MenvR- showed a higher
relative surface expression level than did other Env proteins
(Fig.
1B,
lane 4). However, this would not account for the differences
seen in
syncytium formation, particularly the finding that the
presence of the
R peptide in the chimeric Env proteins affects
syncytium formation only
when Gpr15 is used as the
coreceptor.
One possible mechanism for the fusion inhibition activity of the MuLV R
peptide is that its presence in the cytoplasmic domain
may affect the
folding and conformation of the viral Env proteins.
Studies with
influenza virus HA have shown that it is activated
to induce membrane
fusion through sequential conformational changes
induced by a low pH
(
5,
6). It has been found that there
are two heptad repeat
regions in HA and that they play a critical
role in the conformational
changes and membrane fusion activity
of HA (
6). Such heptad
repeat regions have also been found
in the TM subunit of the HIV, SIV,
and MuLV Env proteins and have
been shown to form a triple-stranded
coiled-coil structure (
6,
8,
16,
39). The discovery of
coreceptors for infection
by HIV and SIV has greatly increased our
understanding of the
mechanism of membrane fusion induced by the HIV
and SIV Env proteins.
By analogy with membrane fusion induced by the
influenza virus
HA protein, it was proposed that the HIV and SIV Env
proteins
first bind to CD4 on cells, which induces a conformational
change
in the Env protein, allowing it to interact with a coreceptor
and resulting in another conformational change and membrane fusion
(
12,
31). Our results suggest that the presence of the MuLV
R peptide profoundly affects the interaction between the external
domain of the SIV Env proteins and the coreceptor Gpr15. Apparently,
binding of the Env protein to CD4 is not affected by the presence
of
the MuLV R peptide, as the R-peptide-containing SIV-MuLV chimeric
Env
proteins can still induce cell fusion in the presence of CCR5.
However,
the presence of the R peptide has an impact on the conformation
of the
chimeric Env proteins, and as a result, their functional
interaction
with the coreceptor Gpr15 is impaired. Alternatively,
it is also
possible that the presence of the R peptide may affect
the affinity of
the Env proteins for both coreceptors CCR5 and
Gpr15. However, the
affinity of the Env proteins for the coreceptor
CCR5 is much stronger,
or less affected by the presence of the
R peptide, than is the affinity
of the Env proteins for the coreceptor
Gpr15. It will be interesting
for future studies to determine
whether the presence of the R peptide
reduces the affinity between
the chimeric Env protein and Gpr15 or if
it prevents the chimeric
Env protein from assuming a fusogenic
conformation upon interaction
with
Gpr15.
Functional studies of the MuLV Env proteins have shown that Env
proteins of different tropism can form heterooligomers and
complement
each other in inducing membrane fusion (
34,
43,
44). In the
studies by Rein et al. (
34), the Env protein of
ecotropic
MuLV with a truncated R peptide was found to form heterooligomers
with
the full-length Env protein of amphotropic MuLV. Such Env
protein
heterooligomers were found to induce fusion in cells expressing
only
the amphotropic MuLV receptor, while each Env protein by
itself failed
to induce any cell fusion. These studies suggested
that truncation of
the MuLV R peptide may render the MuLV Env
protein into a
fusion-competent conformation, while binding to
the receptor is
required to bring the target membrane into its
vicinity. Alternatively,
it is possible that fusion by MuLV Env
proteins may also involve a
secondary coreceptor which is yet
to be identified. Our study suggests
that the interaction between
the MuLV Env protein and its receptor is
similar to the interaction
between the SIV Env protein and its
coreceptors, as indicated
by the similar sensitivities of these Env
proteins to fusion inhibition
by the MuLV R peptide. Future studies on
the mechanism of fusion
inhibition by the MuLV R peptide should further
dissect the process
of membrane fusion induced by viral Env
proteins.
| |
ACKNOWLEDGMENTS |
We thank Tanya Cassingham for help with preparation of the manuscript.
This study was supported by NIH grants CA 18611 and AI 47018.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, 3001 Rollins Research Center, Emory
University School of Medicine, Atlanta, GA 30322. Phone: (404)
727-5947. Fax: (404) 727-8250. E-mail: compans{at}microbio.emory.edu.
| |
REFERENCES |
| 1.
|
Alkhatib, G.,
C. Combadiere,
C. C. Broder,
Y. Feng,
P. E. Kennedy,
P. M. Murphy, and E. A. Berger.
1996.
CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1.
Science
272:1955-1958[Abstract].
|
| 2.
|
Alkhatib, G.,
F. Liao,
E. A. Berger,
J. M. Farber, and K. W. Peden.
1997.
A new SIV co-receptor, STRL33.
Nature
388:238[CrossRef][Medline].
|
| 3.
|
Brody, B. A.,
S. S. Rhee, and E. Hunter.
1994.
Postassembly cleavage of a retroviral glycoprotein cytoplasmic domain removes a necessary incorporation signal and activates fusion activity.
J. Virol.
68:4620-4627[Abstract/Free Full Text].
|
| 4.
|
Bron, R.,
P. J. Klasse,
D. Wilkinson,
P. R. Clapham,
A. Pelchen-Matthews,
C. Power,
T. N. C. Wells,
J. Kim,
S. C. Peiper,
J. A. Hoxie, and M. Marsh.
1997.
Promiscuous use of CC and CXC chemokine receptors in cell-to-cell fusion mediated by a human immunodeficiency virus type 2 envelope protein.
J. Virol.
71:8405-8415[Abstract].
|
| 5.
|
Bullough, P. A.,
F. M. Hughson,
J. J. Skehel, and D. C. Wiley.
1994.
Structure of influenza haemagglutinin at the pH of membrane fusion.
Nature
371:37-43[CrossRef][Medline].
|
| 6.
|
Carr, C. M., and P. S. Kim.
1993.
A spring-loaded mechanism for the conformational change of influenza hemagglutinin.
Cell
73:823-832[CrossRef][Medline].
|
| 7.
|
Chakrabarti, L.,
M. Emerman,
P. Tiollais, and P. Sonigo.
1989.
The cytoplasmic domain of simian immunodeficiency virus transmembrane protein modulates infectivity.
J. Virol.
63:4395-4403[Abstract/Free Full Text].
|
| 8.
|
Chan, D. C.,
D. Fass,
J. M. Berger, and P. S. Kim.
1997.
Core structure of gp41 from the HIV envelope glycoprotein.
Cell
89:263-273[CrossRef][Medline].
|
| 9.
|
Chen, Z.,
P. Zhou,
D. D. Ho,
N. R. Landau, and P. A. Marx.
1997.
Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry.
J. Virol.
71:2705-2714[Abstract].
|
| 10.
|
Deng, H.,
R. Liu,
W. Ellmeier,
S. Choe,
D. Unutmaz,
M. Burkhart,
R. Di Marzio,
S. Marmon,
R. E. Sutton,
C. M. Hill,
C. B. Davis,
S. C. Peiper,
T. J. Schall,
D. R. Littman, and N. R. Landau.
1996.
Identification of a major co-receptor for primary isolates of HIV-1.
Nature
381:661-666[CrossRef][Medline].
|
| 11.
|
Deng, H. K.,
D. Unutmaz,
V. N. KewalRamani, and D. R. Littman.
1997.
Expression cloning of new receptors used by simian and human immunodeficiency viruses.
Nature
388:296-300[CrossRef][Medline].
|
| 12.
|
Doms, R. W., and S. C. Peiper.
1997.
Unwelcomed guests with master keys: how HIV uses chemokine receptors for cellular entry.
Virology
235:179-190[CrossRef][Medline].
|
| 13.
|
Doranz, B. J.,
J. Rucker,
Y. Yi,
R. J. Smyth,
M. Samson,
S. C. Peiper,
M. Parmentier,
R. G. Collman, and R. W. Doms.
1996.
A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors.
Cell
85:1149-1158[CrossRef][Medline].
|
| 14.
|
Dragic, T.,
V. Litwin,
G. P. Allaway,
S. R. Martin,
Y. Hunag,
K. A. Nagashima,
C. Cayanan,
P. A. Maddon,
R. A. Koup,
J. P. Moore, and W. A. Paxton.
1996.
HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5.
Nature
381:667-673[CrossRef][Medline].
|
| 15.
|
Farzan, M.,
H. Choe,
K. Martin,
L. Marcon,
W. Hofmann,
G. Karlsson,
Y. Sun,
P. Barrett,
N. Marchand,
N. Sullivan,
N. Gerard,
C. Gerard, and J. Sodroski.
1997.
Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection.
J. Exp. Med.
186:405-411[Abstract/Free Full Text].
|
| 16.
|
Fass, D.,
S. C. Harrison, and P. S. Kim.
1996.
Retrovirus envelope domain at 1.7 angstrom resolution.
Nat. Struct. Biol.
3:465-469[CrossRef][Medline].
|
| 17.
|
Feng, Y.,
C. C. Broder,
P. E. Kennedy, and E. A. Berger.
1996.
HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor.
Science
272:872-874[Abstract].
|
| 18.
|
Fuerst, T. R.,
E. G. Niles,
F. W. Studier, and B. Moss.
1986.
Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase.
Proc. Natl. Acad. Sci. USA
83:8122-8126[Abstract/Free Full Text].
|
| 19.
|
Gabuzda, D. H.,
A. Lever,
E. Terwilliger, and J. Sodroski.
1992.
Effects of deletions in the cytoplasmic domain on biological functions of human immunodeficiency virus type 1 envelope glycoproteins.
J. Virol.
66:3306-3315[Abstract/Free Full Text].
|
| 20.
|
Green, N.,
T. M. Shinnick,
O. Witte,
A. Ponticelli,
J. G. Sutcliffe, and R. A. Lerner.
1981.
Sequence-specific antibodies show that maturation of Moloney leukemia virus envelope polyprotein involves removal of a COOH-terminal peptide.
Proc. Natl. Acad. Sci. USA
78:6023-6027[Abstract/Free Full Text].
|
| 21.
|
Hallenberger, S.,
V. Bosch,
H. Angliker,
E. Shaw,
H.-D. Klenk, and W. Garten.
1992.
Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160.
Nature
360:358-361[CrossRef][Medline].
|
| 22.
|
Henderson, L. E.,
R. Sowder,
T. D. Copeland,
G. Smythers, and S. Oroszlan.
1984.
Quantitative separation of murine leukemia virus proteins by reversed-phase high-pressure liquid chromatography reveals newly described gag and env cleavage products.
J. Virol.
52:492-500[Abstract/Free Full Text].
|
| 23.
|
Hirsch, V. M.,
P. Edmondson,
M. Murphey-Corb,
B. Arbeille,
P. R. Johnson, and J. L. Mullins.
1989.
SIV adaption to human cells.
Nature
341:573-574[CrossRef][Medline].
|
| 24.
|
Hunter, E., and R. Swanstrom.
1990.
Retrovirus envelope glycoproteins.
Curr. Top. Microbiol. Immunol.
157:187-253[Medline].
|
| 25.
|
Kang, C.-Y.,
K. Hariharan,
M. R. Posner, and P. Nara.
1993.
Identification of a new neutralizing epitope conformationally affected by the attachment of CD4 to gp120.
J. Immunol.
151:449-457[Abstract].
|
| 26.
|
Kodama, T.,
D. P. Wooley,
Y. M. Naidu,
H. W. Kestler III,
M. D. Daniel,
Y. Li, and R. C. Desrosiers.
1989.
Significance of premature stop codons in env of simian immunodeficiency virus.
J. Virol.
63:4709-4714[Abstract/Free Full Text].
|
| 27.
|
Kwong, P.,
R. Wyatt,
J. Robinson,
R. Sweet,
J. Sodroski, and W. Hendrickson.
1998.
Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody.
Nature
393:648-659[CrossRef][Medline].
|
| 28.
|
Lapham, C. K.,
J. Ouyang,
B. Chandrasekhar,
N. Y. Nguyen,
D. S. Dimitrov, and H. Golding.
1996.
Evidence for cell-surface association between fusin and the CD4-gp120 complex in human cell lines.
Science
274:602-605[Abstract/Free Full Text].
|
| 29.
|
Marcon, L.,
H. Choe,
K. A. Martin,
M. Farzan,
P. D. Ponath,
L. Wu,
W. Newman,
N. Gerard,
C. Gerard, and J. Sodroski.
1997.
Utilization of C-C chemokine receptor 5 by the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239.
J. Virol.
71:2522-2527[Abstract].
|
| 30.
|
Martin, K.,
R. Wyatt,
M. Farzan,
H. Choe,
L. Marcon,
E. Desjardins,
J. Robinson,
J. Sodroski,
C. Gerard, and N. P. Gerard.
1997.
CD4-independent binding of SIV gp120 to rhesus CCR5.
Science
278:1470-1473[Abstract/Free Full Text].
|
| 31.
|
Montefiori, D., and J. P. Moore.
1999.
HIV vaccines. Magic or the occult?
Science
283:336-337[Free Full Text].
|
| 32.
|
Ragheb, J. A., and W. F. Anderson.
1994.
pH-independent murine leukemia virus ecotropic envelope-mediated cell fusion: implications for the role of the R peptide and p12E TM in viral entry.
J. Virol.
68:3220-3231[Abstract/Free Full Text].
|
| 33.
|
Rein, A.,
J. Mirro,
J. G. Haynes,
S. M. Ernst, and K. Nagashima.
1994.
Function of the cytoplasmic domain of a retroviral transmembrane protein: p15E-p2E cleavage activates the membrane fusion capability of the murine leukemia virus Env protein.
J. Virol.
68:1773-1781[Abstract/Free Full Text].
|
| 34.
|
Rein, A.,
C. Yang,
J. A. Haynes,
J. Mirro, and R. W. Compans.
1998.
Evidence for cooperation between murine leukemia virus Env molecules in mixed oligomers.
J. Virol.
72:3432-3435[Abstract/Free Full Text].
|
| 35.
|
Ritter, G. D.,
M. J. Mulligan,
S. L. Lydy, and R. W. Compans.
1993.
Cell fusion activity of the simian immunodeficiency virus envelope protein is modulated by the intracytoplasmic domain.
Virology
197:255-264[CrossRef][Medline].
|
| 36.
|
Rucker, J.,
A. L. Edinger,
M. Sharron,
M. Samson,
B. Lee,
J. F. Berson,
Y. Yi,
B. Margulies,
R. G. Collman,
B. J. Doranz,
M. Parmentier, and R. W. Doms.
1997.
Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodeficiency viruses.
J. Virol.
71:8999-9007[Abstract].
|
| 37.
|
Sommerfelt, M. A.,
S. R. Petteway, Jr.,
G. B. Dreyer, and E. Hunter.
1992.
Effect of retroviral proteinase inhibitors on Mason-Pfizer monkey virus maturation and transmembrane glycoprotein cleavage.
J. Virol.
66:4220-4227[Abstract/Free Full Text].
|
| 38.
|
Spies, C. P.,
G. D. Ritter, Jr.,
M. J. Mulligan, and R. W. Compans.
1994.
Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein alters conformation of the external domain.
J. Virol.
68:585-591[Abstract/Free Full Text].
|
| 39.
|
Weissenhorn, W.,
A. Dessen,
S. C. Harrison,
J. J. Skehel, and D. C. Wiley.
1997.
Atomic structure of the ectodomain from HIV-1 gp41.
Nature
387:426-430[CrossRef][Medline].
|
| 40.
|
Willey, R. L.,
J. S. Bonifacino,
B. J. Potts,
M. A. Martin, and R. D. Klausner.
1988.
Biosynthesis, cleavage and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160.
Proc. Natl. Acad. Sci. USA
85:9580-9584[Abstract/Free Full Text].
|
| 41.
|
Wu, L.,
N. P. Gerard,
R. Wyatt,
H. Choe,
C. Parolin,
N. Ruffing,
A. Borsetti,
A. A. Cardoso,
E. Desjardin,
W. Newman,
C. Gerard, and J. Sodroski.
1996.
CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5.
Nature
384:179-183[CrossRef][Medline].
|
| 42.
|
Yang, C., and R. W. Compans.
1996.
Analysis of the cell fusion activities of chimeric simian immunodeficiency virus-murine leukemia virus envelope proteins: inhibitory effects of the R peptide.
J. Virol.
70:248-254[Abstract].
|
| 43.
|
Zhao, Y.,
S. Lee, and W. F. Anderson.
1997.
Functional interactions between monomers of the retroviral envelope protein complex.
J. Virol.
71:6967-6972[Abstract].
|
| 44.
|
Zhao, Y.,
L. Zhu,
C. A. Benedict,
D. Chen,
W. F. Anderson, and P. M. Cannon.
1998.
Functional domains in the retroviral transmembrane protein.
J. Virol.
72:5392-5398[Abstract/Free Full Text].
|
| 45.
|
Zingler, K., and D. R. Littman.
1993.
Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein increases Env incorporation into particles and fusogenicity and infectivity.
J. Virol.
67:2824-2831[Abstract/Free Full Text].
|
Journal of Virology, July 2000, p. 6217-6222, Vol. 74, No. 13
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Wyss, S., Dimitrov, A. S., Baribaud, F., Edwards, T. G., Blumenthal, R., Hoxie, J. A.
(2005). Regulation of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Fusion by a Membrane-Interactive Domain in the gp41 Cytoplasmic Tail. J. Virol.
79: 12231-12241
[Abstract]
[Full Text]
-
Aguilar, H. C., Anderson, W. F., Cannon, P. M.
(2002). Cytoplasmic Tail of Moloney Murine Leukemia Virus Envelope Protein Influences the Conformation of the Extracellular Domain: Implications for Mechanism of Action of the R Peptide. J. Virol.
77: 1281-1291
[Abstract]
[Full Text]
Top
Abstract
Text
