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Journal of Virology, September 2006, p. 8951-8960, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00136-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

DC-SIGN and CLEC-2 Mediate Human Immunodeficiency Virus Type 1 Capture by Platelets

Chawaree Chaipan,1,2 Elizabeth J. Soilleux,3 Peter Simpson,4 Heike Hofmann,1,2,5 Thomas Gramberg,1,2 Andrea Marzi,1,2 Martina Geier,1,2 Elizabeth A. Stewart,6 Jutta Eisemann,7 Alexander Steinkasserer,7 Katsue Suzuki-Inoue,8 Gemma L. Fuller,9 Andrew C. Pearce,9 Steve P. Watson,9 James A. Hoxie,6 Frederic Baribaud,10,{dagger} and Stefan Pöhlmann1,2*

Institute for Clinical and Molecular Virology,1 Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, 91054 Erlangen, Germany,2 Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, United Kingdom,3 Department of Histopathology, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom,4 Department of Medical Microbiology and Virology, University of Kiel, 24105 Kiel, Germany,5 Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,6 Department of Dermatology, University Hospital Erlangen, 91052 Erlangen, Germany,7 Department of Clinical and Laboratory Medicine, Yamanashi University, Yamanashi 409-3898, Japan,8 Centre for Cardiovascular Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom,9 Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104,10

Received 20 January 2006/ Accepted 25 June 2006

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.

* Corresponding author. Mailing address: Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, Glückstraße 6, 91054 Erlangen, Germany. Phone: 49 9131 8529142. Fax: 49 9131 8529111. E-mail: snpoehlm{at}viro.med.uni-erlangen.de.

{dagger} Present address: Incyte Corporation, Wilmington, DE 19880.

Journal of Virology, September 2006, p. 8951-8960, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00136-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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