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Journal of Virology, May 2009, p. 4195-4204, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.00006-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Intercellular Adhesion Molecule 1 (ICAM-1), but Not ICAM-2 and -3, Is Important for Dendritic Cell-Mediated Human Immunodeficiency Virus Type 1 Transmission{triangledown}

Jian-Hua Wang, Constance Kwas, and Li Wu*

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226

Received 2 January 2009/ Accepted 3 February 2009

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.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. Phone: (414) 456-4075. Fax: (414) 456-6535. E-mail: liwu{at}mcw.edu

{triangledown} Published ahead of print on 11 February 2009.

Journal of Virology, May 2009, p. 4195-4204, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.00006-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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