JOURNAL OF VIROLOGY, Nov. 2004, p. 11980–11987
Vol. 78, No. 21
Infection of Specific Dendritic Cells by CCR5-Tropic Human
Immunodeficiency Virus Type 1 Promotes Cell-Mediated Transmission
of Virus Resistant to Broadly Neutralizing Antibodies
Lakshmanan Ganesh,1Kwanyee Leung,1Karin Lore ´,1Reuven Levin,1,2Amos Panet,1,3
Owen Schwartz,1,4Richard A. Koup,1and Gary J. Nabel1*
Vaccine Research Center1and Biological Imaging Facility,4National Institute of Allergy and Infectious Disease,
National Institutes of Health, Bethesda, Maryland, and Department of Infectious Diseases, Israel Institute
for Biological Research, Ness-Ziona,2and Department of Virology, The Hebrew
University–Hadassah Medical School, Jerusalem,3Israel
Received 26 February 2004/Accepted 14 June 2004
The tropism of human immunodeficiency virus type 1 for chemokine receptors plays an important role in the
transmission of AIDS. Although CXCR4-tropic virus is more cytopathic for T cells, CCR5-tropic strains are
transmitted more frequently in humans for reasons that are not understood. Phenotypically immature myeloid
dendritic cells (mDCs) are preferentially infected by CCR5-tropic virus, in contrast to mature mDCs, which are
not susceptible to infection but instead internalize virus into a protected intracellular compartment and
enhance the infection of T cells. Here, we define a mechanism to explain preferential transmission of CCR5-
tropic viruses based on their interaction with mDCs and sensitivity to neutralizing antibodies. Infected
immature mDCs differentiated normally and were found to enhance CCR5-tropic but not CXCR4-tropic virus
infection of T cells even in the continuous presence of neutralizing antibodies. Infectious synapses also formed
normally in the presence of such antibodies. Infection of immature mDCs by CCR5-tropic virus can therefore
establish a pool of infected cells that can efficiently transfer virus at the same time that they protect virus from
antibody neutralization. This property of DCs may enhance infection, contribute to immune evasion, and could
provide a selective advantage for CCR5-tropic virus transmission.
Dendritic cells (DCs) normally circulate throughout tissues
and lymphoid organs, where they capture antigens and process
them for presentation to the immune system (reviewed in ref-
erence 40). DCs also capture both CCR5- and CXCR4-tropic
viruses efficiently and transmit them to T cells (19, 21, 26). The
envelope (Env) glycoprotein of human immunodeficiency virus
type 1 (HIV-1) (gp120) is highly glycosylated, and virus attach-
ment to DCs is mediated largely through mannose-specific
C-type lectin receptor DC-SIGN (12, 19, 27, 43, 44, 49). Virus
bound to DC-SIGN is internalized into distinct cellular com-
partments and can remain infectious for several days. HIV-1
uses a specific cell contact, termed the infectious synapse (31),
to facilitate delivery to CD4?lymphocytes, resulting in en-
hanced viral replication in DC-CD4?lymphocyte cocultures.
Geijtenbeek et al. observed that HIV does not infect mono-
cyte-derived DCs, but the virus is captured by DC-SIGN and
transferred to CD4?T cells by a mechanism called trans-
infection. Other reports have suggested that immature DCs
must be infected to transmit virus (5, 20, 45), although it has
been difficult to demonstrate productive infection of DCs both
in vitro (3, 6–8, 19, 21) and in vivo (38). Monoclonal antibodies
(MAbs) can block both virus entry and transmission of HIV
from monocyte-derived DCs to T cells during trans-infection,
but it is unclear whether such MAbs can inhibit transfer after
productive infection of immature DCs or by mature DCs.
The aim of the present study was to characterize the trans-
mission of CXCR4- and CCR5-tropic viruses to immature and
mature myeloid DCs (mDCs) and to define the sensitivity of
DC-mediated virus infection to neutralizing antibodies. Our
findings confirm and extend previous observations: immature
mDCs are shown to be preferentially infected by CCR5-tropic
virus (5, 20, 35, 45), whereas mature mDCs are not susceptible
to infection by either type of virus. Infected immature mDCs
differentiated normally and enhanced CCR5-tropic but not
CXCR4-tropic virus infection of T cells even in the continuous
presence of neutralizing antibodies, indicating that mDCs con-
fer resistance to HIV-1 inactivation through this previously
unrecognized mechanism of antibody resistance.
MATERIALS AND METHODS
Cell preparation and analysis. Human T-cell leukemia cell lines A3R5 (a
subline of CEM expressing both CCR5 and CXCR4) and MT-2 expressing
CXCR4 were kindly provided by John Mascola. mDCs and autologous CD4?T
cells were purified from elutriated monocytes and lymphocytes prepared from
healthy adult donors by a two-step procedure consisting of automated leuka-
pheresis and counterflow centrifugal elutriation at the Transfusion Medicine
Department of Warren Grant Magnuson Clinical Center, National Institutes of
Health, Bethesda, Md. (1). Blood mDCs were isolated from the elutriated mono-
cyte fraction by deletion of cells expressing BDCA-4 and CD9 by using mi-
crobeads (Miltenyi Biotech, Auburn, Calif.) and positive selection by using an-
tibodies to CD1c (Miltenyi Biotech). CD4?T cells were isolated from the
lymphocyte fraction by negative selection with a CD4?T-cell isolation kit (Mil-
tenyi Biotech). mDCs CD4?T lymphocytes, and the T-cell lines were grown in
RPMI 1640 medium supplemented with 10% fetal bovine serum, penicillin, and
streptomycin. Primary CD4?T cells were stimulated with phytohemagglutinin A
(PHA; 10 ?g/ml; Calbiochem)–interleukin-2 (IL-2; 20 U/ml; PeproTech) for 24 h
and maintained in medium supplemented with IL-2 (20 U/ml). mDCs were
cultured in medium containing granulocyte-macrophage colony-stimulating fac-
* Corresponding author. Mailing address: Vaccine Research Center,
NIAID, National Institutes of Health, Bldg. 40, Rm. 4502, MSC-3005,
40 Convent Dr., Bethesda, MD 20892-3005. Phone: (301) 496-1852.
Fax: (301) 480-0274. E-mail: email@example.com.
tor (10 ng/ml; PeproTech). To initiate differentiation of DCs, cells were treated
with poly(I-C) (50 ng/ml; Sigma) for 48 h (9). Antibodies to CD11c and CD14
(BD Pharmingen) were used to assess the purity of DCs and antibodies to CD40,
CD80, CD86, and HLA-DR (BD Pharmingen) were used to characterize the
differentiation of DCs by flow cytometry.
Viruses. Pseudotyped HIV IIIB and ADA lentivirus expressing luciferase were
prepared by transient cotransfection of 293T cells with calcium phosphate (In-
vitrogen). Briefly, the packaging vector pMD8.2, pHR-Luciferase, and the en-
velope expressing vector pSVIII-ADA (10) or pRSV-IIIB were transiently trans-
fected into 293T cells (33). Supernatants were harvested 48 and 72 h after
transfection, filtered, and stored at ?80°C. The virus concentration was deter-
mination by an enzyme-linked immunosorbent assay for the p24 antigen
(Coulter). Green fluorescent protein (GFP)-Vpr-labeled HIV-1 was produced by
transfection of HEK 293 T cells with pLAI provirus and the plasmid pEGFP-C3
(Clontech, Palo Alto, Calif.) containing the entire Vpr coding region fused to the
carboxy terminus of eGFP (GFP-Vpr), which was a generous gift from Thomas
Hope (30). Cells were washed at 16 to 20 h posttransfection and replenished with
fresh medium. After 48 h, the supernatants were harvested, filtered through a
0.45-?m syringe filter, and concentrated. Briefly, 32 ml of supernatant was
layered on 5 ml of Optiprep (Iodoxinal) medium (Invitrogen, Carlsbad, Calif.)
and centrifuged at 50,000 ? g for 1.5 h with a Surespin 630 rotor (Sorvall,
Newtown, Conn.). The last 3 ml of supernatant remaining above the OptiPrep
interface was collected and frozen at ?80°C in 500-?l aliquots. Concentrated
wild-type HIV stocks were prepared in peripheral blood mononuclear cells and
were kindly provided by John Mascola and Mark Louder.
Flow cytometry. For antibody neutralization assays, primary T cells were col-
lected 48 h after incubation with infected DCs. These cells were stained with
CD3 phycoerythrin (PE), CD11c APC, and ethidium bromide monoazide (EMA)
for 10 min. EMA was cross-linked onto the cells by exposing them to a bright
light source for 15 min. Cells were washed once, fixed and permeabilized with
Cytoperm/Cytofix (BD Pharmingen) for 20 min. Cells were then stained for p24
Gag (KC-57 FITC; Coulter) for 20 min and washed once in 1? Perm/Wash
buffer (BD Pharmingen). The percentage of T cells that received virus from DC
without antibody ranged from 0.5 to 6% of T cells infected with HIV-1, as
measured by p24 in the single-round replication assay, and varied according to
the donor. The percent neutralization was defined as a reduction in the
number of p24-Ag-positive cells compared to the number in control wells with
no antibody (29).
To assess HIV infection and DC maturation, cells were stained with CD80 PE,
CD11c APC, or EMA as described above. Fixed and permeabilized cells were
then stained for p24 Gag. All flow cytometry was done by using a four-color
FACSCalibur (BD Biosciences), and data analysis was done by using FloJo (Tree
Lentivirus infections and luciferase assays. mDCs were plated in 96-well
White View plates (Packard) after isolation and either maintained in culture or
differentiated and infected with lentiviruses as described above. For direct in-
fections of DC, cells were incubated for another 48 h. To measure transfer of
IIIB and ADA lentivirus, DC cells were mixed with T cells (MT2 or A3R5) for
48 h (26). Antibodies were added at various time points as described in the figure
legends. After 48 h, the cells were lysed in the plates with 20 ?l of cell lysis buffer
(Promega) for 5 to 10 min. Then, 100 ?l of luciferin substrate (Promega) was
added to the wells with a multichannel pipette, followed by immediate assay for
luminescence by using a 96-well plate luminometer (Packard).
Confocal microscopy. mDCs (105) isolated from human elutriated monocytes
were plated onto 12-well plates. After 24 to 48 h, they were infected with HIV-1
labeled with Vpr-GFP for 30 min. Cells were washed, detached with trypsin-
EDTA, washed again, and added to T cells (3 ? 104cells/well) plated onto
eight-well coverslip slides (Nalge Nunc). Uptake, polarization, and transfer were
assessed in the presence of b12 or a control antibody starting immediately after
the addition of infected mDCs to T cells by confocal microscopy. Images of live
FIG. 1. HIV infection of mDCs. (A) Direct viral infection by replication-defective HIV reporter viruses of mDCs (left and middle) and T cells
(A3R5; right). Untreated mDCs and poly(I-C)-treated mDCs (3 ? 104cells) were infected with either HIV-1ADA(left) or HIV-1IIIB(middle) (25
ng of p24) for 2 h. A3R5 T cells (3 ? 104cells) were also infected with HIV-1ADAor HIV-1IIIB(25 ng of p24) for 2 h (right). Cells washed three
times and maintained in cell culture were collected 2 days later for luciferase assay. (B) Direct viral infection of mDCs by CXCR4-tropic (X4),
CCR5-tropic (R5), and dualtropic (Dual), HIV-1 isolates. mDCs (3 ? 105/well) isolated from a single donor elutriated monocytes (see Materials
and Methods) were mock infected or infected with the indicated HIV-1 strains for 12 h, washed, incubated for 48 h, and analyzed by
fluorescence-activated cell sorting for intracellular p24 after gating to exclude EMA and to select for CD11c cells.
VOL. 78, 2004DCs, IMMUNE EVASION, AND TRANSMISSION OF HIV11981
cells were obtained every 2 min for 1 h. Multiple fields were sampled, and
representative images were recorded. The DC-T-cell synapses in the presence of
control or b12 antibody were quantified as follows: the number of DCs labeled
with the HIV-1 Vpr-GFP virus and the numbers of DC-T cell synapses in each
of the 10 fields were counted and are represented as a ratio of DC-T cell synapses
versus total labeled DCs. There were 168 labeled cells in the control antibody,
and 12 of them formed synapses with the T cells (7.1%). In the b12 group, there
were 172 labeled cells, 14 of which formed synapses with T cells (8.1%) (P ? 0.5
[Student t test]).
HIV Infection in mDCs. To characterize mDC infection,
immature mDCs were isolated and infected with virus. Cells
with an immature phenotype, i.e., ?90% CD3?, CD14?,
CD15?, CD19?, CD56?, and CD11c?HLA-DR?, were isolat-
ed and characterized. Treatment of these cells with poly(I-C)
resulted in ?95% mDCs that upregulated CD40, CD80, CD86,
and HLA-DR glycoprotein expression consistent with a ma-
ture phenotype, as previously described (4, 22, 39). Immature
or poly(I-C)-treated mDCs were transduced with luciferase-
expressing HIV vectors (33) that use CCR5- (HIV-1ADA) or
CXCR4-tropic (HIV-1IIIB) envelopes (Env). Immature mDCs
were more readily tranduced by CCR5-tropic virus than were
poly(I-C)-treated mDCs (Fig. 1A, left panel), but neither cell
type could be transduced with CXCR4-tropic HIV-1IIIBvirus
(Fig. 1A, middle panel), though T cells were readily infected by
both viruses (Fig. 1A, right panel). To confirm this finding in
additional strains and with replication-competent virus, wild-
type HIV CCR5-tropic or CXCR4-tropic virus strains were
prepared and used to infect immature mDCs. Virus replication
was assessed by using a single-step growth assay for intracel-
lular Gag protein described previously (29). In contrast to
CXCR4 and a dualtropic virus, CCR5-tropic HIV-1 infected
immature mDCs (Fig. 1B).
Maturation of mDCs after HIV infection. The ability of
infected immature mDCs to differentiate was assessed with
wild-type CCR5-tropic HIV-1BaL. Cells infected with HIV-
1BaLbut treated with zidovudine (AZT) served as a negative
control, and an aliquot of each was treated with poly(I-C) for
48 h after HIV-1 infection. Cells in each group were analyzed
by flow cytometry for intracellular HIV-1 p24, CD11c, and
either CD80 or CD40 DC maturation markers after dead cells
were excluded by their affinity for EMA. Immature DCs in-
fected with HIV were able to mature and display the charac-
teristic dendritic cell maturation markers CD40 and CD80
(Fig. 2) comparably to HIV-1-infected AZT-treated mDCs in
both poly(I-C)-treated (right lower panel) and untreated
groups (right upper panel). Notably, immature DCs infected
with HIV that were subsequently matured with poly(I-C) were
able to transfer the virus to T cells more efficiently than im-
mature infected DCs (Fig. 3A).
Effect of antibody exposure on trans-infection. To determine
whether virus sequestration by mature mDCs could affect the
sensitivity of HIV to neutralization by antibodies, virus transfer
studies were next performed in mature mDCs with two well-
characterized potent broadly neutralizing antibodies, 2F5 and
b12, that inactivate both primary and laboratory-adapted
HIV-1 isolates (11, 15, 34, 42). b12 binds to gp120 and blocks
the virus from attaching to CD4 or chemokine receptors (37,
50, 51). 2F5 recognizes an epitope on the transmembrane
subunit gp41 (32, 36) and does not prevent HIV-1 cell attach-
FIG. 2. Infection with HIV-1BaLdoes not prevent maturation of mDCs by poly(I-C). mDCs (3 ? 105/well) isolated from a single donor
elutriated monocytes (see Materials and Methods) were infected with HIV-1BaL(2 ?g of p24/ml). The control groups were treated with AZT (10
?M; left top and bottom panels) to prevent HIV replication. One set of control and HIV-infected cells (left lower panel, second lower panel) were
matured 48 h after infection with poly(I-C) (50 ?g/ml). To determine the relationship between infection and maturation, CD80 and CD40
expression (in separate experiments) were assessed in the Gag?population compared to the Gag?population in untreated (right upper) and
poly(I-C)-treated (right lower) groups of DCs.
11982GANESH ET AL.J. VIROL.
ment but inhibits HIV entry, presumably by interfering with
fusion process (34). Poly(I-C)-treated mDCs were exposed to
HIV-1BaLfor 2 h, washed, and incubated with 2F5 or b12 for
30 min or 48 h with autologous PHA–IL-2-stimulated T cells.
Compared to a control group incubated with 2F5 antibody
prior to infection, virus neutralization was almost completely
ineffective at the time of transfer by mDCs, and b12 efficacy
was also substantially reduced (Fig. 3B). In this assay, a frac-
tion of the virus is transferred to the T cells by formation of the
infectious synapse at any 30-min interval, and therefore the
virus became more sensitive to neutralization over time. How-
ever, a percentage of this CCR5-tropic virus remained resistant,
19% with 2F5 and 18% with b12, even after 48 h of antibody
exposure (Fig. 3B). This finding was observed in independent ex-
periments on DCs and T cells from different donors, suggesting
that CCR5-tropic virus can escape neutralization in DCs.
Effect of antibody exposure on cell-mediated transfer from
HIV-1-infected mDCs. During trans-infection, a significant
fraction of virus was not inactivated even after 48 h of antibody
exposure in a single-round replication assay. The effect of
broadly neutralizing antibodies on viral replication in primary
human DCs and T cells over extended times was therefore
assessed. In one set of experiments, CXCR4-tropic virus HIV-
1IIIB, CCR5-tropic virus HIV-1BaL, or dualtropic virus HIV-
189.6were neutralized with b12 for an hour before they infected
T cells (Fig. 4A) or mature mDCs (Fig. 4B). In another set of
experiments, these viruses were used to infect mature mDCs
washed and incubated with T cells in the presence of b12
continuously (Fig. 4C). In contrast to virus incubated with
antibody before infection in the absence of mDC, CCR5-tropic
virus, which appeared to be completely neutralized 2 days after
infection, as previously described (18), unexpectedly grew ex-
ponentially after an initial lag phase (Fig. 4A versus 4C, middle
panel). In contrast, CXCR4-tropic virus was completely inac-
tivated by the b12 antibody (Fig. 4A versus 4C, left panel). A
dualtropic virus, HIV-189.6, behaved similarly to the CXCR4-
tropic virus but was incompletely inactivated by b12 in the
presence of infected mDCs (Fig. 4A versus 4C, right panel).
When the virus is neutralized by b12 antibody, it is unable to
infect T cells, but the same virus, when passaged through DCs,
was able to establish a productive infection upon transfer to T
cells after an initial lag phase (Fig. 4A versus 4B). When the
ability of b12 antibody to reduce “infectious synapse” forma-
tion was analyzed with a GFP-labeled HIV (31), no inhibition
was seen (Fig. 5A, 7.1% [control] versus 8.1% [b12]; P ? 0.5).
Taken together, these data suggest that infection of mDCs by
CCR5-tropic virus, in combination with uptake by these cells,
provides a mechanism for evading the antibody response and
enhance infection of T cells.
Inactivation of HIV-1 by neutralizing antibodies at the time
of initial exposure would provide a potent mechanism to in-
hibit HIV infection in vivo and would be a desirable feature of
an immune response elicited by a highly effective AIDS vac-
cine, but HIV has evolved a number of mechanisms to evade
broadly neutralizing antibodies. For example, HIV Env can
evade this response through carbohydrate and variable loop
masking, conformational changes that protect highly con-
served, receptor binding structures, and its high degree of
genetic variability (47). Here we report that immunoglobulin G
neutralizing antibodies can block CCR5-tropic HIV-1 entry
into myeloid DCs, but once the virus is internalized through
DC-SIGN by the antigen-presenting cell, it provides a previ-
ously unrecognized mechanism of immune evasion to neutral-
izing antibodies that may also be integral to the strategy of
HIV spread and persistence. The enhancement of infection
and the protection from neutralizing antibodies provided by
the DCs help the virus to efficiently infect host T cells (Fig. 4A
Recently, McDonald et al. have described the formation of
FIG. 3. Effect of antibody exposure on HIV-1 trans-infection. (A)
HIV-1BaL-infected immature DCs transfer the virus more effectively to
T cells upon maturation. mDCs (3 ? 105/well) isolated from a single
donor (elutriated monocytes) were mock infected or infected with
HIV-1BaL(2 ?g of p24/ml). One set of mock-infected and HIV-in-
fected mDCs was matured 48 h after infection with poly(I-C) (50 ?g/
ml). After 48 h, primary PHA–IL-2-stimulated autologous CD4?T
cells were added to both mock-infected and HIV-1-infected immature
and mature mDCs, followed by incubation in the presence of indinavir
(1 ?M) for another 48 h. Cells were then assayed for intracellular Gag
by flow cytometry. (B) Poly(I-C)-treated mDCs were infected with
HIV-1BaLfor 2 h, washed five times, and incubated with the indicated
concentrations of 2F5 (left) or b12 (right) and primary PHA–IL-2-
stimulated autologous CD4?T cells for 30 min or 48 h. In the control
group, the virus was preincubated with antibody for 30 min prior to
infection of CD4?T cells for 2 h. Cells were maintained in indinavir (1
?M), and p24 Gag in CD3?CD11c?cells was assayed by fluorescence-
activated cell sorting 48 h later. Percent neutralization was defined as
the reduction in the number of p24-Ag-positive cells compared to the
number in control wells with no antibody (29).
VOL. 78, 2004DCs, IMMUNE EVASION, AND TRANSMISSION OF HIV11983
an infectious synapse, which provides both a structure and a
mechanism to explain the enhancement of T-cell infection by
DCs (31). The present study is consistent with this model and
further suggests that such a synapse is poorly accessible to
neutralizing antibodies (Fig. 5A). In the seven viruses tested
(two CXCR4-tropic, three CCR5-tropic, and two dualtropic),
it was found that once CCR5-dependent viruses establish DC
infection, even the most potent broadly neutralizing antibodies
are limited in their ability to prevent the T-cell spread of
infection (Fig. 4C). This phenomenon is likely reflective of
primary HIV-1 strains that are also generally resistant to an-
tibody neutralization (34). These findings suggest that in in-
fected individuals, mDCs may serve as a reservoir and immune
therapies for HIV will need to prevent or reduce the infection
of these cells to be highly effective.
Several groups have shown that DC-mediated trans-infec-
tion can be inhibited by both neutralizing antibodies and fusion
inhibitors with different R5 isolates (18, 25). The findings here
are consistent with previous work; however, there has been no
analysis of the effect of DCs on neutralizing antibodies in
long-term DC–T-cell cocultures. The present study shows that
even in the continuous presence of neutralizing antibodies,
mDCs confer resistance to HIV-1 inactivation by known,
broadly neutralizing antibodies. This finding contrasts with the
effect of peptide-based fusion inhibitors, which inhibit viral
replication during trans-infection (25), suggesting that these
lower-molecular-weight, more-diffusible antagonists are able
to gain access to virus in DCs. The present study also points to
at least two additional mechanisms by which mDCs may en-
hance HIV infection and transmission. The ability of CCR5-
tropic viruses to infect immature DCs, although not highly
productive (Fig. 1B), allows the development of a reservoir of
FIG. 4. mDCs infected with HIV-1BaLconfer resistance to antibody neutralization. Wild-type HIV-1IIIB, HIV-1BaL,or HIV-189.6(12 ng of p24)
was exposed to anti-gp120 antibody, b12 (50 ?g/ml), for 60 min before infection of T cells (A) or mDCs (B) (4 ? 104cells each) for 2 h.
(C) Alternatively, these viruses were used to infect mDCs (4 ? 104cells each) for 2 h. Cells were washed five times to remove virus and either
incubated with T cells alone (105cells) (B) or treated with b12 (50 ?g/ml) and T cells (105cells) (C). b12 was added every 60 h and left in the
DC–T-cell mixture for the duration of the experiments (C). At the appropriate time, cell supernatants were collected, and p24 ELISA was
performed as instructed by the manufacturer (Coulter). The data are representative of duplicate experiments.
11984 GANESH ET AL. J. VIROL.
infected mDCs that infect T cells efficiently upon maturation
(Fig. 1B, 3A, and 4B). Although previous studies have ad-
dressed the infectivity of monocyte-derived DCs by HIV (13,
14, 16–18, 20, 21, 23, 46), it has not been evident why CCR5-
tropic virus remains more highly transmissible than the
CXCR4-tropic virus. One explanation is suggested by prefer-
ential infection of immature mDCs by CCR5-tropic virus,
which may serve as a cellular “Trojan horse” that initiates a
persistent infection (Fig. 5B). This property, as well as the
enhanced infectivity, suggests that DCs may play a major role
in HIV pathogenesis and transmission. These findings also
suggest that a preventive vaccine should be able to elicit robust
antibodies to inactivate the virus before the antigen-presenting
cell can internalize it. Finally, it has been recognized that DC
bind to other viruses, such as Ebola virus (2, 28), dengue virus
(41), cytomegalovirus (24), and severe acute respiratory syn-
drome virus (48), through DC-SIGN or related receptors; this
mechanism of viral uptake and protection from antibodies may
be relevant to other infectious diseases.
We thank Tina Suhana and Ati Tislerics for help with manuscript
preparation, John Mascola and Mark Louder for advice and assistance
with neutralization assays, Karen Stroud for figure preparation, and
members of the Nabel lab for helpful discussions.
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