title: Lentivirus degradation and DC-SIGN expression by human platelets and megakaryocytes.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Département d'Hématologie, Institut Cochin, INSERM U567, Paris and Faculté de médecine, Paris-Ile de France-Ouest, France.
authors.forename: S
authors.initials: S
authors.lastname: Boukour
authors.forename: J-M
authors.initials: JM
authors.lastname: Massé
authors.forename: L
authors.initials: L
authors.lastname: Bénit
authors.forename: A
authors.initials: A
authors.lastname: Dubart-Kupperschmitt
authors.forename: E M
authors.initials: EM
authors.lastname: Cramer
mesh_terms: D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D004705:Endocytosis; D015870:Gene Expression; D015752:Genes, env; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics / Q000276:immunology; D016086:Lentivirus / Q000235:genetics / Q000472:pathogenicity*; D008533:Megakaryocytes / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology*; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics / Q000276:immunology; D011991:Receptors, Virus / Q000097:blood / Q000235:genetics; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin