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

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2006 Aug 31

PMID 16940507

Citations 122

Authors

Chawaree Chaipan

Elizabeth J Soilleux

Peter Simpson

Heike Hofmann

Thomas Gramberg

Andrea Marzi

Martina Geier

Elizabeth A Stewart

Jutta Eisemann

Alexander Steinkasserer

Katsue Suzuki-Inoue

Gemma L Fuller

Andrew C Pearce

Steve P Watson

James A Hoxie

Frederic Baribaud

Stefan Pohlmann

Affiliations

Soon will be listed here.

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.

Citing Articles

Dengue virus infection: how platelet-leukocyte crosstalk shapes thrombotic events and inflammation.

Amin A, Nikdoust F, Khorram S, Marashi S, Ghanavati P, Ameri F Mol Biol Rep. 2025; 52(1):119.

PMID: 39804486 DOI: 10.1007/s11033-025-10222-x.

Characterization of Platelet Receptors and Their Involvement in Immune Activation of These Cells.

Tokarz-Deptula B, Baraniecki L, Palma J, Stosik M, Deptula W Int J Mol Sci. 2024; 25(23).

PMID: 39684330 PMC: 11641666. DOI: 10.3390/ijms252312611.

Hyperexpression of and as Possible Platelet Risk Biomarkers in Patients With COVID-19.

DE Oliveira Sales L, DA Silva J, DE Pinho Pessoa F, Dias Nogueira B, DE Oliveira L, Khayat A In Vivo. 2024; 38(6):2853-2863.

PMID: 39477442 PMC: 11535951. DOI: 10.21873/invivo.13766.

Comparative Effects of Efavirenz and Dolutegravir on Metabolomic and Inflammatory Profiles, and Platelet Activation of People Living with HIV: A Pilot Study.

Roux C, Mason S, du Toit L, Nel J, Rossouw T, Steel H Viruses. 2024; 16(9).

PMID: 39339938 PMC: 11437493. DOI: 10.3390/v16091462.

Beyond basic characterization and omics: Immunomodulatory roles of platelet-derived extracellular vesicles unveiled by functional testing.

Palviainen M, Puutio J, Ostergaard R, Eble J, Maaninka K, Butt U J Extracell Vesicles. 2024; 13(10):e12513.

PMID: 39330919 PMC: 11428872. DOI: 10.1002/jev2.12513.

References

Voulgaropoulou F, Pontow S, Ratner L . Productive infection of CD34+-cell-derived megakaryocytes by X4 and R5 HIV-1 isolates. Virology. 2000; 269(1):78-85. DOI: 10.1006/viro.2000.0193. View

Youssefian T, Drouin A, Masse J, Guichard J, Cramer E . Host defense role of platelets: engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Blood. 2002; 99(11):4021-9. DOI: 10.1182/blood-2001-12-0191. View

ODoherty U, Swiggard W, Malim M . Human immunodeficiency virus type 1 spinoculation enhances infection through virus binding. J Virol. 2000; 74(21):10074-80. PMC: 102046. DOI: 10.1128/jvi.74.21.10074-10080.2000. View

Limmer A, Ohl J, Kurts C, Ljunggren H, Reiss Y, Groettrup M . Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance. Nat Med. 2000; 6(12):1348-54. DOI: 10.1038/82161. View

Pohlmann S, Soilleux E, Baribaud F, Leslie G, Morris L, Trowsdale J . DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans. Proc Natl Acad Sci U S A. 2001; 98(5):2670-5. PMC: 30196. DOI: 10.1073/pnas.051631398. View

Geijtenbeek T, Krooshoop D, Bleijs D, van Vliet S, van Duijnhoven G, Grabovsky V . DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol. 2001; 1(4):353-7. DOI: 10.1038/79815. View

Pohlmann S, Baribaud F, Lee B, Leslie G, Sanchez M, Munch J . DC-SIGN interactions with human immunodeficiency virus type 1 and 2 and simian immunodeficiency virus. J Virol. 2001; 75(10):4664-72. PMC: 114220. DOI: 10.1128/JVI.75.10.4664-4672.2001. View

Nardi M, Tomlinson S, Greco M, Karpatkin S . Complement-independent, peroxide-induced antibody lysis of platelets in HIV-1-related immune thrombocytopenia. Cell. 2001; 106(5):551-61. DOI: 10.1016/s0092-8674(01)00477-9. View

Baribaud F, Pohlmann S, Sparwasser T, Kimata M, Choi Y, Haggarty B . Functional and antigenic characterization of human, rhesus macaque, pigtailed macaque, and murine DC-SIGN. J Virol. 2001; 75(21):10281-9. PMC: 114602. DOI: 10.1128/JVI.75.21.10281-10289.2001. View

10.

Wu L, Martin T, Vazeux R, Unutmaz D, KewalRamani V . Functional evaluation of DC-SIGN monoclonal antibodies reveals DC-SIGN interactions with ICAM-3 do not promote human immunodeficiency virus type 1 transmission. J Virol. 2002; 76(12):5905-14. PMC: 136240. DOI: 10.1128/jvi.76.12.5905-5914.2002. View

11.

Baribaud F, Pohlmann S, Leslie G, Mortari F, Doms R . Quantitative expression and virus transmission analysis of DC-SIGN on monocyte-derived dendritic cells. J Virol. 2002; 76(18):9135-42. PMC: 136426. DOI: 10.1128/jvi.76.18.9135-9142.2002. View

12.

Baribaud F, Doms R, Pohlmann S . The role of DC-SIGN and DC-SIGNR in HIV and Ebola virus infection: can potential therapeutics block virus transmission and dissemination?. Expert Opin Ther Targets. 2002; 6(4):423-31. DOI: 10.1517/14728222.6.4.423. View

13.

Turville S, Cameron P, Handley A, Lin G, Pohlmann S, Doms R . Diversity of receptors binding HIV on dendritic cell subsets. Nat Immunol. 2002; 3(10):975-83. DOI: 10.1038/ni841. View

14.

Hsu M, Harouse J, Gettie A, Buckner C, Blanchard J, Cheng-Mayer C . Increased mucosal transmission but not enhanced pathogenicity of the CCR5-tropic, simian AIDS-inducing simian/human immunodeficiency virus SHIV(SF162P3) maps to envelope gp120. J Virol. 2002; 77(2):989-98. PMC: 140803. DOI: 10.1128/jvi.77.2.989-998.2003. View

15.

Simmons G, Reeves J, Grogan C, Vandenberghe L, Baribaud F, Whitbeck J . DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology. 2002; 305(1):115-23. DOI: 10.1006/viro.2002.1730. View

16.

Pohlmann S, Zhang J, Baribaud F, Chen Z, Leslie G, Lin G . Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. J Virol. 2003; 77(7):4070-80. PMC: 150620. DOI: 10.1128/jvi.77.7.4070-4080.2003. View

17.

Gardner J, Durso R, Arrigale R, Donovan G, Maddon P, Dragic T . L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus. Proc Natl Acad Sci U S A. 2003; 100(8):4498-503. PMC: 153584. DOI: 10.1073/pnas.0831128100. View

18.

McDonald D, Wu L, Bohks S, KewalRamani V, Unutmaz D, Hope T . Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science. 2003; 300(5623):1295-7. DOI: 10.1126/science.1084238. View

19.

Lozach P, Lortat-Jacob H, de Lacroix de Lavalette A, Staropoli I, Foung S, Amara A . DC-SIGN and L-SIGN are high affinity binding receptors for hepatitis C virus glycoprotein E2. J Biol Chem. 2003; 278(22):20358-66. DOI: 10.1074/jbc.M301284200. View

20.

van Kooyk Y, Geijtenbeek T . DC-SIGN: escape mechanism for pathogens. Nat Rev Immunol. 2003; 3(9):697-709. DOI: 10.1038/nri1182. View