DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets.
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.
Chaipan
Chawaree
C
Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
Soilleux
Elizabeth J
EJ
Simpson
Peter
P
Hofmann
Heike
H
Gramberg
Thomas
T
Marzi
Andrea
A
Geier
Martina
M
Stewart
Elizabeth A
EA
Eisemann
Jutta
J
Steinkasserer
Alexander
A
Suzuki-Inoue
Katsue
K
Fuller
Gemma L
GL
Pearce
Andrew C
AC
Watson
Steve P
SP
Hoxie
James A
JA
Baribaud
Frederic
F
Pöhlmann
Stefan
S
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
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