title: DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets.
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.
authors.affiliation: Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
authors.forename: Chawaree
authors.initials: C
authors.lastname: Chaipan
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Soilleux
authors.forename: Peter
authors.initials: P
authors.lastname: Simpson
authors.forename: Heike
authors.initials: H
authors.lastname: Hofmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Gramberg
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzi
authors.forename: Martina
authors.initials: M
authors.lastname: Geier
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Stewart
authors.forename: Jutta
authors.initials: J
authors.lastname: Eisemann
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinkasserer
authors.forename: Katsue
authors.initials: K
authors.lastname: Suzuki-Inoue
authors.forename: Gemma L
authors.initials: GL
authors.lastname: Fuller
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Pearce
authors.forename: Steve P
authors.initials: SP
authors.lastname: Watson
authors.forename: James A
authors.initials: JA
authors.lastname: Hoxie
authors.forename: Frederic
authors.initials: F
authors.lastname: Baribaud
authors.forename: Stefan
authors.initials: S
authors.lastname: Pöhlmann
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000821:virology; D015658:HIV Infections / Q000097:blood; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D037181:Lectins, C-Type / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008533:Megakaryocytes / Q000821:virology; D008562:Membrane Glycoproteins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C104778:CLEC2B protein, human