Differential transmission of human immunodeficiency virus type 1 by distinct subsets of effector dendritic cells

J Virol. 2002 Aug;76(15):7812-21. doi: 10.1128/jvi.76.15.7812-7821.2002.

Abstract

Dendritic cells (DC) support human immunodeficiency virus type 1 (HIV-1) transmission by capture of the virus particle in the mucosa and subsequent transport to the draining lymph node, where HIV-1 is presented to CD4(+) Th cells. Virus transmission involves a high-affinity interaction between the DC-specific surface molecule DC-SIGN and the viral envelope glycoprotein gp120 and subsequent internalization of the virus, which remains infectious. The mechanism of viral transmission from DC to T cells is currently unknown. Sentinel immature DC (iDC) develop into Th1-promoting effector DC1 or Th2-promoting DC2, depending on the activation signals. We studied the ability of these effector DC subsets to support HIV-1 transmission in vitro. Compared with iDC, virus transmission is greatly upregulated for the DC1 subset, whereas DC2 cells are inactive. Increased transmission by DC1 correlates with increased expression of ICAM-1, and blocking studies confirm that ICAM-1 expression on DC is important for HIV transmission. The ICAM-1-LFA-1 interaction is known to be important for immunological cross talk between DC and T cells, and our results indicate that this cell-cell contact is exploited by HIV-1 for efficient transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication
  • Cell Differentiation*
  • Dendritic Cells / cytology
  • Dendritic Cells / virology*
  • HIV Infections / transmission*
  • HIV-1 / physiology*
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Phenotype
  • T-Lymphocytes / virology*

Substances

  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1