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J Virol. 2009 May;83(9):4195-204. doi: 10.1128/JVI.00006-09. Epub 2009 Feb 11.

Intercellular adhesion molecule 1 (ICAM-1), but not ICAM-2 and -3, is important for dendritic cell-mediated human immunodeficiency virus type 1 transmission.

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1
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. liwu@mcw.edu

Abstract

Dendritic cells (DCs) play a critical role in cell-to-cell-mediated transmission of human immunodeficiency virus type 1 (HIV-1). Interactions between intercellular adhesion molecules (ICAMs) and their ligands facilitate DC-T-cell contact. The interaction between ICAM-1 on DCs and leukocyte function-associated molecule 1 (LFA-1) on CD4(+) T cells has been proposed to be important for DC-mediated HIV-1 transmission. Given that DCs and T cells express multiple ICAMs and binding ligands, the relative importance of ICAMs in DC-mediated HIV-1 transmission remains to be defined. Here, we examine the role of ICAM-1, -2, and -3 in DC-mediated HIV-1 transmission to various types of target cells including primary CD4(+) T cells. The expression levels of ICAMs and their ligands on immature and mature DCs and various types of HIV-1 target cells were measured by flow cytometry. Blocking ICAM-1 in DCs with specific monoclonal antibodies and small interfering RNA impaired DC-mediated HIV-1 transmission. DC-mediated viral transmission was significantly inhibited when both ICAM-1 on DCs and LFA-1 on CD4(+) T cells were blocked. However, blockade of ICAM-1 on target cells did not significantly inhibit DC-mediated HIV-1 transmission. Ectopic expression and antibody blocking suggest that DC-mediated HIV-1 transmission to primary CD4(+) T cells is independent of ICAM-2 and ICAM-3. Taken together, our data clarified the role of ICAMs in DC-mediated HIV-1 transmission to CD4(+) T cells.

PMID:
19211748
PMCID:
PMC2668448
DOI:
10.1128/JVI.00006-09
[Indexed for MEDLINE]
Free PMC Article
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