J Virol, June 1998, p. 5251-5255, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Actin-Dependent Receptor Colocalization Required
for Human Immunodeficiency Virus Entry into Host Cells
Sujatha
Iyengar,1
James E. K.
Hildreth,1 and
David H.
Schwartz2,*
Department of Pharmacology and Molecular
Sciences, School of Medicine,1 and
Department of Molecular Microbiology and Immunology, School of
Hygiene and Public Health,2 The Johns Hopkins
University, Baltimore, Maryland 21205
Received 23 October 1997/Accepted 3 March 1998
 |
ABSTRACT |
Human immunodeficiency virus (HIV) envelope binds CD4 and a
chemokine receptor in sequence, releasing hydrophobic viral gp41 residues into the target membrane. HIV entry required actin-dependent concentration of coreceptors, which could be disrupted by cytochalasin D (CytoD) without an effect on cell viability or mitosis. Pretreatment of peripheral blood mononuclear cells, but not virus, inhibited entry
and infection. Immunofluorescent confocal microscopy of activated cells
revealed CD4 and CXCR4 in nonoverlapping patterns. Addition of gp120
caused polarized cocapping of both molecules with subsequent pseudopod
formation, while CytoD pretreatment blocked these membrane changes
completely.
| |
TEXT |
Elucidation of the mechanism of
virus selection of, and entry into, suitable host cells is a key to
understanding human immunodeficiency virus (HIV) transmission and
pathogenesis. Recent major advances have been the identification of
fusin (CXCR4) and various 
-chemokine receptors (CKRs [CCR5 and
CCR3]) as coreceptors for T-cell line-adapted (TCLA) and
macrophage-tropic strains of HIV-1, respectively (2, 4, 5, 7,
10-12, 15, 23). Additional cellular and herpesvirus-encoded CKR-like molecules supporting dual tropism have recently been described
(21, 24). Regardless of the coreceptor utilized, sequential
binding of gp120 to CD4, followed by interaction of newly exposed
and/or stabilized envelope regions with the CKR (28), is
postulated to cause conformational changes allowing cryptic regions of
transmembrane gp41 to insert into target membranes and mediate fusion
with virus or infected cells.
CXC and CC family CKRs are 7-transmembrane domain G protein-coupled
molecules capable of transducing activation signals. Recognition of
this fact led to investigation of the role of receptor signaling in HIV
infection. Results with cytoplasmic tail truncation and cytoplasmic
domain mutants (22) suggested that the signaling function of
coreceptors is dispensable with respect to viral entry. However, a role
for energy-dependent homotypic and/or heterotypic clustering of
receptors was not ruled out. Furthermore, those experiments were
carried out with tumor cell lines that are constitutively activated and
may not fully reflect the entry requirements for normal lymphocytes. We
therefore examined the role of energy-dependent, actin-dependent cell
surface aggregation of HIV receptors as a determinant of virion entry
into CD4+ CKR-expressing peripheral blood mononuclear cells
(PBMCs).
Phytohemagglutinin (PHA)-activated PBMCs were exposed to 0.2 and 1.0 µM cytochalasin D (CytoD; Aldrich, Milwaukee, Wis.) for 1 h and
washed free of drug prior to exposure to 104 50% tissue
culture infective doses (TCID50) of TCLA
HIV-1MN (Advanced Biotechnologies, Inc., Columbia, Md.).
CytoD specifically impairs F-actin polymerization in the cytoskeleton
(30). While higher concentrations (20 to 40 µM) of CytoD
have been used to inhibit antigen induced actin-mediated surface
immunoglobulin (Ig) patching and capping on B cells (26),
lower concentrations are adequate to inhibit membrane ruffling (8,
31). In our experiments, 0.2 to 1.0 µM CytoD, continuously
present, had no effect on PBMC viability or proliferation (not shown).
Nevertheless, 1 h of pretreatment with 0.2 and 1.0 µM CytoD
resulted in, respectively, 95 and 98% inhibition of viral growth 7 days after infection (Fig. 1). Similar results were obtained with TCLA HIV-1IIIB and
macrophage-tropic HIV-1BaL (not shown). HIV-1MN
infection is completely blocked in this system by the anti-CD4
monoclonal antibody (MAb) SIM7 developed in our laboratory, as shown
previously (18).
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FIG. 1.
Effect of transient treatment of CytoD on infection of
PHA-activated PBMCs by HIV-1MN T-cell-tropic virus.
Pretreatment was for 1 h at CytoD concentrations of 0.2 and 1 µM
and exposed to 104 TCID50 of
HIV-1MN for 1 h at 37°C. The cells were washed free
of virus and drug and incubated at 37°C. Culture supernatants were
assayed for p24 by EIA (Organon Teknika, Durham, N.C.) on day 7. Results represent the mean ± standard error (SEM) of three
independent experiments.
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|
To rule out an additional effect of CytoD on virus budding, activated
PBMCs were exposed to 104 TCID50 of
HIV-1MN for 24 h and then treated with 10 µM
zidovudine (AZT) to prevent subsequent rounds of infection. Cells
washed free of virus after an additional 24 h and maintained for 7 days in 10 µM AZT plus CytoD (0.2 or 1.0 µM) showed no significant reduction in virion budding (Fig. 2). One
hour of pretreatment of 106 TCID50
HIV-1MN with 5.0 µM CytoD had no antiviral effect when virus and drug were subsequently diluted 100-fold for use in culture (not shown).
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FIG. 2.
Effect of continuous treatment of CytoD on virus budding
from PHA-activated PBMCs. Cells exposed to 104
TCID50 of HIV-1MN for 24 h at 37°C were
then treated with 10 µM AZT for an additional 24 h, washed, and
maintained in medium containing AZT and CytoD at 37°C. Supernatants
were assayed for p24 on day 7. Results represent the mean ± standard error (SEM) of three independent experiments.
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Blockage of HIV infection in CytoD-treated cells appeared to be at the
level of virion entry following CD4 binding, as demonstrated by
decreased internalized p24 protein within 3 h of exposure to virus
(Fig. 3) and decreased frequency of DNA
PCR env signal in replicate 12,500-cell aliquots (8 of 10 versus 1 of 10, P < 0.01) at 16 h (Fig.
4). In these experiments, noninternalized
virions were removed by trypsinization (19) prior to DNA PCR
and the p24 enzyme immunoassay (EIA). To control for incomplete
trypsinization of noninternalized virus giving a false-positive signal,
PHA-activated cells incubated in medium alone or 1 µM CytoD for
1 h were exposed to virus at 4°C to allow for virus binding
without internalization. In some cases, cells were also pretreated with
25 µM AZT overnight to prevent reverse transcription of virus that
may have been internalized even at 4°C. To rule out nonspecific
sticking of virus to cells, additional controls included cells exposed
to heat-inactivated virus (56°C for 3 h). All controls were
negative for internalized p24 (Fig. 3) and for env signal in
DNA PCR. HLA-DR was successfully amplified in parallel for all aliquots
to confirm the presence of template (not shown).
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FIG. 3.
Viral entry assay of CytoD-treated (1.0 µM) or
untreated PHA-activated PBMCs after exposure to 105
TCID50 of HIV-1MN. After this initial
incubation of 1 h at 37°C, cells were washed free of virus and
drug, incubated for an additional 2 h, and treated with 0.25%
trypsin for 5 min at 37°C. Internalized p24 in cell lysates was
measured by EIA. Control cells were mock infected, exposed to virus at
4°C to control for nontrypsinized virus on cell surface, or exposed
to heat-inactivated virus.
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FIG. 4.
PCR-based limiting dilution analysis of HIV DNA in
CytoD-treated or untreated PBMCs. Cells (10 × 106)
pretreated with complete medium (A) or 1 µM CytoD (B) were exposed to
105 TCID50 of HIV-1MN for 1 h
at 37°C, washed, and incubated at 37°C for 3 h to allow for
virus internalization. Noninternalized virus was trypsinized. Cells
were treated with 100 U of DNase (Boehringer Mannheim, Indianapolis,
Ind.) per ml in the presence of 10 mM MgCl2 for 30 min at
37°C, washed, and maintained in complete medium at 37°C for an
additional 8 h. Twofold-serially-diluted aliquots were amplified
with nested primer pairs for the HIV-1 env region as
described previously (27), and 10 replicates at each
dilution were analyzed for signal. The endpoints for untreated and
CytoD-treated cells were 3,000 and 12,500 cells, respectively. The
presence (+) or absence ( ) of amplified signal (HIV-1MN)
from 12,500 cells is indicated under each aliquot lane. M, marker
DNA.
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|
Confocal immunofluorescence microscopy was used to visualize the effect
of 5 µg of HIV-1IIIB gp120 envelope protein (Genentech) per ml on cell surface CXCR4 and CD4 in the presence or absence of
CytoD. Two MAbs, FSN-M2 (IgG1 [J. E. K. Hildreth]) and 12G5 (IgG2a [14]), recognizing CXCR4 were used with similar
results. SIM7, an anti-CD4 MAb that does not compete with gp120 for
binding to CD4, was used. Different isotype specificities and
preadsorption of secondary antibodies minimized cross-reactivity. All
primary antibodies were used at 2.5 µg/ml, and fluorescein
isothiocyanate- or Texas red-conjugated secondary antibodies from
Southern Biotechnology Associates (Birmingham, Ala.) were used at 10 µg/ml. Specificity of labeling and absence of signal crossover were
established by examination of single-labeled control samples.
In the absence of gp120, CD4 and CXCR4 maintained a diffusely punctate
surface staining pattern with minimal overlap on PHA-activated cells.
Addition of gp120 at 37°C resulted in aggregation of both receptors
in overlapping patches by 45 min and complete coreceptor colocalization
in a polarized pattern at 60 min. Interestingly, with an increased
incubation time of 90 min, a pseudopod was seen to form from the region
of cells where receptors had polarized. Pretreatment of cells with 1 µM CytoD for 1 h abrogated these gp120-induced surface events
(Fig. 5).
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FIG. 5.
Actin-dependent colocalization of surface CD4 and CXCR4,
visualized by confocal immunofluorescence microscopy. A diffusely
punctate distribution of CD4 (green) and CXCR4 (red) is seen 30 min
after addition of HIV-1IIIB rgp120 (A). Colocalized
coreceptors appear as a false yellow polarized cap by 45 min (B), and
by 90 min, a pseudopod has started to form from the area of receptor
colocalization (C). Following 1 h of transient pretreatment with
CytoD (1 µM), cells exhibit no changes from the baseline distribution
of CD4 and CXCR4 in the presence of gp120 over 90 min (D). In the
absence of gp120 or CytoD pretreatment, occasional cells may start to
form homotypic polarized aggregates of CXCR4 which do not involve CD4
colocalization and produce no yellow overlap (E). Essentially identical
patterns were seen with MAb 12G5 (not shown). Scale bar, 2.5 µm.
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Cellular adhesion molecules are known to cluster at the surface of
pseudopods and play a role in cell migration (9). The emergence of pseudopods from the area in which CD4 and chemokine receptors polarize is suggestive of a chemotactic response to soluble
envelope (29) and may reflect additional interactions with
cell surface adhesion molecules (19a).
There are two broad interpretations of these data which are not
mutually exclusive. Coclustering of CD4-CKR heterodimers may provide a
critical density necessary for each gp120 monomer of the trimeric
envelope spike to bind a CKR at the same time. This would be important
if conformational changes releasing all three gp41 domains
simultaneously were required for high-efficiency entry. This would be
analogous to density thresholds demonstrated for adhesion molecule
interactions and T-cell receptor triggering (13).
Alternatively or additionally, cocapping of receptors may transduce
activation signals important for some as yet undefined actin-dependent
steps. Cocapping-induced signals may be less crucial for infection of
constitutively activated transformed human cells. This would explain
the absence of coreceptor polarization in recent studies of
CD4+ mink lung cells, although localized copatching was
observed (28). Neither of these interpretations requires the
assumption that individual CD4-coreceptor heterodimers are completely
absent from the cell surface prior to contact with HIV envelope.
Previous findings of the temperature dependence of virion entry have
generally been interpreted as a reflection of lipid bilayer mobility
thermodynamics; however, energy-dependent cytoskeletal movement is also
temperature sensitive and could explain decreased viral entry at 4°C
(16, 17).
Regardless of the exact mechanisms by which receptor clustering enables
viral entry, the dependence on intact cytoskeleton contraction has
implications for host cell selection beyond selective coreceptor usage.
In order to replicate efficiently, HIV virions must enter mononuclear
cells that are sufficiently activated to provide phosphorylated
nucleotides for reverse transcription and energy-dependent transport of
the preintegration complex into the nucleus. Once integrated, the
provirus depends on host cells to produce progeny before their demise
or elimination. Greater than 90% of CD4+ cells are
quiescent in a healthy individual and therefore are less than ideal
hosts for HIV. Moreover, >90% of activated lymphocytes are destined
for programmed cell death, with a life span roughly equal to the HIV
minimum generation time (1, 32). Also, HIV may replicate in
the setting of cell lysis and fragmentation, which releases membrane
vesicles which may bear CD4 and CKRs (3).
Faced with a multitude of inappropriate potential host cells and cell
fragments, the ability to enter only cells which are viable and
activated would be a major selective advantage. Caspase-mediated activation of a p21-activated kinase, PAK2, is implicated in the dysregulation of cytoskeletal actin very early in the course of apoptosis (25). If coreceptor clustering requires both
activated cytoskeletal contraction and an intact cell membrane free of
early apoptotic changes, it could serve as an indicator of host
fitness, which the virus probes interactively prior to entry.
This model makes several experimentally verifiable predictions. (i)
Rigorously purified quiescent cells expressing CD4 and CKRs and cells
in the early stages of apoptosis will fail to exhibit receptor
clustering upon interaction with HIV envelope and will be only
minimally permissive for entry of CD4-bound virions. Recently reported
studies support the resistance to infection of highly purified resting
cells (6). (ii) HIV which does not enter such cells will
remain infectious for suitable hosts, including formerly quiescent
cells which become activated within a short period of binding virus.
(iii) HIV mutants which make use of a single receptor or are otherwise
independent of cytoskeletal activation will not be pathogenic or
replication competent in vivo unless they are also capable of
activating quiescent cells upon binding. Experiments are under way to
test these hypotheses. Our results may be generalizable to other
viruses. Murine ecotropic retrovirus receptors actively cluster, and
Kizhatil and Albritton have recently shown that entry can be blocked by
CytoD (20).
| |
ACKNOWLEDGMENTS |
We thank J. A. Hoxie for 12G5 antibody, J. Mitchell and R. Hampton for technical help, and M. Delannoy for assistance with confocal microscopy.
This work was supported in part by NIH grant 2RO1 AI31806-05 and by
American Cancer Society grant IRG 11-36.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Molecular Microbiology and Immunology, Johns Hopkins School of Hygiene and Public Health, 615 N. Wolfe St., Baltimore, MD 21205. Phone: (410)
955-3175. Fax: (410) 955-0105. E-mail: dschwart{at}jhsph.edu.
| |
REFERENCES |
| 1.
|
Ahmed, R., and D. Gray.
1996.
Immunological memory and protective immunity: understanding their relation.
Science
272:54-60[Abstract].
|
| 2.
|
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-1 alpha, MIP-1 beta receptor as a fusion cofactor for macrophage-tropic HIV-1.
Science
272:1955-1958[Abstract].
|
| 3.
|
Aupeix, K.,
B. Hugel,
T. Martin,
P. Bischoff,
H. Lill,
J.-L. Pasqualli, and J.-M. Freyssinet.
1997.
The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection.
J. Clin. Invest.
99:1546-1554[Medline].
|
| 4.
|
Bleul, C. C.,
M. Farzan,
H. Choe,
C. Parolin,
I. Clark-Lewis,
J. Sodroski, and T. A. Springer.
1996.
The lymphocyte chemoattractant SDF-1 is a ligand for lestr/fusin and blocks HIV-1 entry.
Nature (London)
382:829-833[Medline].
|
| 5.
|
Choe, H.,
M. Farzan,
Y. Sun,
N. Sullivan,
B. Rollins,
P. D. Ponath,
L. Wu,
C. R. Mackay,
G. LaRosa,
W. Newman,
N. Gerard,
C. Gerard, and J. Sodroski.
1996.
The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates.
Cell
85:1135-1148[Medline].
|
| 6.
|
Chou, C.-S.,
O. Ramilo, and E. S. Vitetta.
1997.
Highly purified CD25() resting T cells cannot be infected de novo with HIV-1.
Proc. Natl. Acad. Sci. USA
94:1361-1365[Abstract/Free Full Text].
|
| 7.
|
Cocchi, F.,
A. L. DeVico,
A. Garzino-Demo,
S. K. Arya,
R. C. Gallo, and P. Lusso.
1995.
Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells.
Science
270:1811-1815[Abstract/Free Full Text].
|
| 8.
|
Cooper, J. A.
1987.
Effect of cytochalasin and phalloidin on actin.
J. Cell Biol.
105:1473-1478[Free Full Text].
|
| 9.
|
Del Pozo, M. A.,
P. Sanchez-Mateos,
M. Nieto, and F. Sanchez-Madrid.
1995.
Chemokines regulate cellular polarization and adhesion receptor redistribution during lymphocyte interaction with endothelium and extracellular matrix. Involvement of cAMP signaling pathway.
J. Cell Biol.
131:495-508[Abstract/Free Full Text].
|
| 10.
|
Deng, H.,
R. Liu,
W. Ellmeier,
S. Choe,
D. Unutmaz,
M. Burkhart,
P. 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[Medline].
|
| 11.
|
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[Medline].
|
| 12.
|
Dragic, T.,
V. Litwin,
G. P. Allaway,
S. R. Martin,
Y. Huang,
K. A. Nagashima,
C. Cayanan,
P. J. 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[Medline].
|
| 13.
|
Dustin, M. L.,
L. M. Ferguson,
P.-Y. Chan,
T. A. Springer, and D. E. Golan.
1996.
Visualization of CD2 interaction with LFA3 and determination of two-dimensional dissociation constant for adhesion receptors in a contact area.
J. Cell Biol.
132:465-474[Abstract/Free Full Text].
|
| 14.
|
Enders, M. J.,
P. R. Clapham,
M. Marsh,
M. Ahuja,
J. D. Turner,
A. McKnight,
J. F. Thomas,
B. Stoebenauhaggarty,
S. Choe,
P. J. Vance,
T. N. C. Wells,
C. A. Power,
S. S. Sutterwala,
R. W. Doms,
N. R. Landau, and J. A. Hoxie.
1996.
CD4-independent infection by HIV-2 is mediated by fusin/CXCR4.
Cell
87:745-756[Medline].
|
| 15.
|
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
272:872-877[Abstract].
|
| 16.
|
Frey, S.,
M. Marsh,
S. Günther,
A. Pelchen-Matthews,
P. Stephens,
S. Ortlepp, and T. Stegmann.
1995.
Temperature dependence of cell-cell fusion induced by the envelope glycoprotein of human immunodeficiency virus type 1.
J. Virol.
69:1462-1472[Abstract].
|
| 17.
|
Fu, Y.-K.,
T. K. Hart,
Z. L. Jonak, and P. J. Bugelski.
1993.
Physicochemical dissociation of CD4-mediated syncytium formation and shedding of human immunodeficiency virus type 1 gp120.
J. Virol.
67:3818-3825[Abstract/Free Full Text].
|
| 18.
|
Gomez, M. B., and J. E. K. Hildreth.
1995.
Antibody to adhesion molecule LFA-1 enhances plasma neutralization of human immunodeficiency virus type 1.
J. Virol.
69:4628-4632[Abstract].
|
| 19.
|
Himathongkham, S., and P. A. Luciw.
1996.
Restriction of HIV-1 (subtype B) replication at the entry step in rhesus macaque cells.
Virology
219:485-488[Medline].
|
| 19a.
| Iyengar, S., D. H. Schwartz, and J. E. K. Hildreth. Submitted for publication.
|
| 20.
|
Kizhatil, K., and L. M. Albritton.
1997.
Requirements of different components of the host cell cytoskeleton distinguish ecotropic murine leukemia virus entry via endocytosis from entry via surface fusion.
J. Virol.
71:7145-7156[Abstract].
|
| 21.
|
Liao, F.,
G. Alkhatib,
K. W. C. Peden,
G. Sharma,
E. A. Berger, and J. M. Farber.
1997.
STRL33, a novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1.
J. Exp. Med.
185:2015-2023[Abstract/Free Full Text].
|
| 22.
|
Lu, Z.-H.,
J. F. Berson,
Y.-H. Chen,
J. D. Turner,
T.-Y. Zhang,
M. Sharron,
M. H. Jenks,
Z.-X. Wang,
J. Kim,
J. Rucker,
J. A. Hoxie,
S. C. Peiper, and R. W. Doms.
1997.
Evolution of HIV-1 coreceptor usage through interactions with distinct CCR5 and CXCR4 domains.
Proc. Natl. Acad. Sci. USA
94:6426-6431[Abstract/Free Full Text].
|
| 23.
|
Oberlin, E.,
A. Amara,
F. Bachelerie,
C. Bessia,
J. L. Virelizier,
F. Arenzana-Seisdedos,
O. Schwartz,
J. M. Heard,
I. Clark-Lewis,
D. F. Legler,
M. Loetscher,
M. Baggiolini, and B. Moser.
1996.
The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1.
Nature
382:833-835[Medline].
|
| 24.
|
Pleskoff, O.,
C. Treboute,
A. Brelot,
N. Heveker,
M. Seman, and M. Alizon.
1997.
Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry.
Science
276:1874-1878[Abstract/Free Full Text].
|
| 25.
|
Rudel, T., and G. M. Bokoch.
1997.
Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2.
Science
276:1571-1574[Abstract/Free Full Text].
|
| 26.
|
Schliwa, M.
1982.
Action of cytochalasin D on cytoskeletal networks.
J. Cell Biol.
92:79-91[Abstract/Free Full Text].
|
| 27.
|
Schwartz, D. H.,
U. Sharma,
M. Busch,
K. Weinhold,
T. Matthews,
J. Lieberman,
D. Brix,
H. Farzadegan,
J. Margolick,
T. Quinn,
B. Davis,
O. Bagasra,
R. Pomerantz, and R. Viscidi.
1994.
Absence of replicating infectious virus and unique immune response in an asymptomatic HIV+ long-term survivor.
AIDS Res. Hum. Retroviruses
12:1703-1711.
|
| 28.
|
Ugolini, S.,
M. Moulard,
I. Mondor,
N. Barois,
D. Demandolx,
J. Hoxie,
A. Brelot,
M. Alizon,
J. Davoust, and Q. J. Sattentau.
1997.
HIV-1 gp120 induces an association between CD4 and the chemokine receptor CXCR4.
J. Immunol.
159:3000-3008[Abstract].
|
| 29.
|
Weissman, D.,
R. L. Rabin,
J. Arthos,
A. Rubbert,
M. Dybul,
R. Swofford,
S. Venkatesan,
J. M. Farber, and A. S. Fauci.
1997.
Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor.
Nature
389:981-985[Medline].
|
| 30.
|
Wessels, N.,
B. Spooner,
J. Ash,
H. Bradley,
M. Iuduena,
E. Taylor,
J. Wrenn, and K. Yamada.
1971.
Microfilaments in cellular and developmental processes.
Science
171:135-143[Abstract/Free Full Text].
|
| 31.
|
Yahara, I.,
F. Harada,
S. Sekita,
K. Yoshihira, and S. Natori.
1982.
Correlation between effects of 24 different cytochalasins on cellular structures and cellular events and those on actin in vivo.
J. Cell Biol.
92:69-78[Abstract/Free Full Text].
|
| 32.
|
Zinkernagel, R. M.
1996.
Immunology taught by viruses.
Science
271:173-178[Abstract].
|
J Virol, June 1998, p. 5251-5255, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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