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

Jian-Hua Wang1, Constance Kwas, Li Wu

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

Journal of Virology
|February 13, 2009
PubMed

Insights

Intercellular adhesion molecule-1 (ICAM-1) on dendritic cells (DCs) is crucial for human immunodeficiency virus type 1 (HIV-1) transmission to CD4(+) T cells. Blocking ICAM-1 on DCs, but not target cells, significantly inhibits HIV-1 spread.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Dendritic cells (DCs) are key mediators of human immunodeficiency virus type 1 (HIV-1) cell-to-cell transmission.
  • Intercellular adhesion molecules (ICAMs) facilitate DC-T-cell interactions, potentially influencing HIV-1 spread.
  • The specific roles of ICAM-1, ICAM-2, and ICAM-3 in DC-mediated HIV-1 transmission require clarification.

Purpose of the Study:

  • To investigate the distinct roles of ICAM-1, ICAM-2, and ICAM-3 in dendritic cell-mediated HIV-1 transmission to CD4(+) T cells.
  • To determine the impact of blocking ICAMs on DCs and target cells on HIV-1 transmission efficiency.

Main Methods:

  • Flow cytometry was used to quantify ICAM expression on immature and mature DCs and HIV-1 target cells.
  • Monoclonal antibodies and small interfering RNA were employed to block ICAM-1 function on DCs.
  • Blocking experiments were conducted on both DCs and target cells, including primary CD4(+) T cells.

Main Results:

  • Blocking ICAM-1 on dendritic cells significantly impaired HIV-1 transmission.
  • Simultaneous blockade of ICAM-1 on DCs and LFA-1 on CD4(+) T cells markedly inhibited viral transmission.
  • Blocking ICAM-1 on target CD4(+) T cells did not significantly affect DC-mediated HIV-1 transmission.
  • ICAM-1, but not ICAM-2 or ICAM-3, was identified as critical for DC-mediated HIV-1 transmission to CD4(+) T cells.

Conclusions:

  • ICAM-1 on dendritic cells is a critical factor for efficient HIV-1 transmission to CD4(+) T cells.
  • Target cell ICAM-1 expression is not essential for this transmission pathway.
  • These findings elucidate the specific contribution of ICAMs in the context of HIV-1 spread via dendritic cells.

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