期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 200, 期 10, 页码 1279-1288出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20041356
关键词
HIV/SIV; virological synapse; RNA interference; lentiviral vectors; trans infection
Dendritic cells (DCs) are essential for the early events of human immuno deficiency 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.
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