DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets

J Virol. 2006 Sep;80(18):8951-60. doi: 10.1128/JVI.00136-06.

Abstract

Platelets can engulf human immunodeficiency virus type 1 (HIV-1), and a significant amount of HIV-1 in the blood of infected individuals is associated with these cells. However, it is unclear how platelets capture HIV-1 and whether platelet-associated virus remains infectious. DC-SIGN and other lectins contribute to capture of HIV-1 by dendritic cells (DCs) and facilitate HIV-1 spread in DC/T-cell cocultures. Here, we show that platelets express both the C-type lectin-like receptor 2 (CLEC-2) and low levels of DC-SIGN. CLEC-2 bound to HIV-1, irrespective of the presence of the viral envelope protein, and facilitated HIV-1 capture by platelets. However, a substantial fraction of the HIV-1 binding activity of platelets was dependent on DC-SIGN. A combination of DC-SIGN and CLEC-2 inhibitors strongly reduced HIV-1 association with platelets, indicating that these lectins are required for efficient HIV-1 binding to platelets. Captured HIV-1 was maintained in an infectious state over several days, suggesting that HIV-1 can escape degradation by platelets and might use these cells to promote its spread. Our results identify CLEC-2 as a novel HIV-1 attachment factor and provide evidence that platelets capture and transfer infectious HIV-1 via DC-SIGN and CLEC-2, thereby possibly facilitating HIV-1 dissemination in infected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / virology*
  • Cell Adhesion Molecules / physiology*
  • Cell Line
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Dendritic Cells / virology
  • HIV Infections / blood
  • HIV-1 / metabolism*
  • Humans
  • Jurkat Cells
  • Lectins, C-Type / physiology*
  • Leukocytes, Mononuclear / virology
  • Megakaryocytes / virology
  • Membrane Glycoproteins / physiology*
  • Receptors, Cell Surface / physiology*

Substances

  • CLEC2B protein, human
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Receptors, Cell Surface