PMID- 15545354
OWN - NLM
STAT- MEDLINE
DCOM- 20050204
LR  - 20181113
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 200
IP  - 10
DP  - 2004 Nov 15
TI  - DC-SIGN-mediated infectious synapse formation enhances X4 HIV-1 transmission from 
      dendritic cells to T cells.
PG  - 1279-88
AB  - Dendritic cells (DCs) are essential for the early events of human 
      immunodeficiency virus (HIV) infection. Model systems of HIV sexual transmission 
      have shown that DCs expressing the DC-specific C-type lectin DC-SIGN capture and 
      internalize HIV at mucosal surfaces and efficiently transfer HIV to CD4+ T cells 
      in lymph nodes, where viral replication occurs. Upon DC-T cell clustering, 
      internalized HIV accumulates on the DC side at the contact zone (infectious 
      synapse), between DCs and T cells, whereas HIV receptors and coreceptors are 
      enriched on the T cell side. Viral concentration at the infectious synapse may 
      explain, at least in part, why DC transmission of HIV to T cells is so 
      efficient.Here, we have investigated the role of DC-SIGN on primary DCs in X4 
      HIV-1 capture and transmission using small interfering RNA-expressing lentiviral 
      vectors to specifically knockdown DC-SIGN. We demonstrate that DC-SIGN- DCs 
      internalize X4 HIV-1 as well as DC-SIGN+ DCs, although binding of virions is 
      reduced. Strikingly, DC-SIGN knockdown in DCs selectively impairs infectious 
      synapse formation between DCs and resting CD4+ T cells, but does not prevent the 
      formation of DC-T cells conjugates. Our results demonstrate that DC-SIGN is 
      required downstream from viral capture for the formation of the infectious 
      synapse between DCs and T cells. These findings provide a novel explanation for 
      the role of DC-SIGN in the transfer and enhancement of HIV infection from DCs to 
      T cells, a crucial step for HIV transmission and pathogenesis.
FAU - Arrighi, Jean-Francois
AU  - Arrighi JF
AD  - Dept. of Dermatology and Venereology, University Hospital of Geneva, 4-752, 24 
      Rue Micheli-du-Crest, 1211 Geneva, Switzerland.
FAU - Pion, Marjorie
AU  - Pion M
FAU - Garcia, Eduardo
AU  - Garcia E
FAU - Escola, Jean-Michel
AU  - Escola JM
FAU - van Kooyk, Yvette
AU  - van Kooyk Y
FAU - Geijtenbeek, Teunis B
AU  - Geijtenbeek TB
FAU - Piguet, Vincent
AU  - Piguet V
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Lectins, C-Type)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Antibodies, Monoclonal
MH  - Binding Sites
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cells, Cultured
MH  - Dendritic Cells/metabolism/*virology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Genetic Vectors
MH  - HIV Infections/metabolism/*transmission
MH  - HIV-1/*metabolism
MH  - Humans
MH  - Lectins, C-Type/*metabolism
MH  - Lentivirus/genetics
MH  - Microscopy, Fluorescence
MH  - RNA, Small Interfering/genetics
MH  - Receptors, Cell Surface/*metabolism
MH  - T-Lymphocytes/metabolism/*virology
PMC - PMC2211914
EDAT- 2004/11/17 09:00
MHDA- 2005/02/05 09:00
PMCR- 2005/05/15
CRDT- 2004/11/17 09:00
PHST- 2004/11/17 09:00 [pubmed]
PHST- 2005/02/05 09:00 [medline]
PHST- 2004/11/17 09:00 [entrez]
PHST- 2005/05/15 00:00 [pmc-release]
AID - jem.20041356 [pii]
AID - 20041356 [pii]
AID - 10.1084/jem.20041356 [doi]
PST - ppublish
SO  - J Exp Med. 2004 Nov 15;200(10):1279-88. doi: 10.1084/jem.20041356.