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

C Chaipan, EJ Soilleux, P Simpson, H Hofmann… - Journal of …, 2006 - Am Soc Microbiol
C Chaipan, EJ Soilleux, P Simpson, H Hofmann, T Gramberg, A Marzi, M Geier, EA Stewart…
Journal of virology, 2006Am Soc Microbiol
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 …
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.
American Society for Microbiology