Lentivirus degradation and DC-SIGN expression by human platelets and megakaryocytes

J Thromb Haemost. 2006 Feb;4(2):426-35. doi: 10.1111/j.1538-7836.2006.01749.x.

Abstract

Background and aim: As platelets are able to endocytose human immunodeficiency virus (HIV), we have investigated the fate of lentiviruses when endocytosed by human platelets and megakaryocytes (MK), and have characterized a specific receptor directly involved in this function.

Methods: Genetically modified (non-replicative) lentiviruses with an HIV envelope (HIV-e) or with a vesicular stomatitis virus protein G envelope (VSV-e) were alternatively used and their interaction with platelets and MK analyzed by electron microscopy (EM) and immunoEM.

Results: When incubated with platelets, HIV-e and VSV-e lentiviruses were internalized in specific endocytic vesicles and trafficked to the surface connected canalicular system (SCCS). Double immunolabeling for the viral P24 core protein and alpha-granule markers showed that lentiviruses were degraded in the SCCS after contact with alpha-granule proteins. In culture MK, lentiviruses were found in endocytic vesicles and accumulated in acid phosphatase-containing multivesicular bodies (MVB). The expression of the pathogen receptor dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN) was then demonstrated in platelets by flow cytometry, immunoEM and Western blot. Anti-DC-SIGN antibodies decreased HIV-e lentivirus internalization by platelets, showing that the receptor is functional. Specific signals for DC-SIGN protein and mRNA were also found in MK.

Conclusion: This study indicates that platelets and MK can internalize lentiviruses in a pathway, which either provide a shelter to lentiviral particles or alternatively disrupts viral integrity. The receptor DC-SIGN is involved in this function.

MeSH terms

  • Antibodies, Monoclonal
  • Base Sequence
  • Blood Platelets / metabolism*
  • Blood Platelets / ultrastructure
  • Blood Platelets / virology*
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / blood*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology
  • DNA, Complementary / genetics
  • Endocytosis
  • Gene Expression
  • Genes, env
  • Genetic Vectors
  • HIV-1 / genetics
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Lectins, C-Type / antagonists & inhibitors
  • Lectins, C-Type / blood*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology
  • Lentivirus / genetics
  • Lentivirus / pathogenicity*
  • Megakaryocytes / metabolism*
  • Megakaryocytes / ultrastructure
  • Megakaryocytes / virology*
  • Microscopy, Electron
  • RNA, Messenger / blood
  • RNA, Messenger / genetics
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / blood*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Virus / blood
  • Receptors, Virus / genetics
  • Vesicular stomatitis Indiana virus / genetics

Substances

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • DNA, Complementary
  • Lectins, C-Type
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Virus