Activation of human platelets through gp140, the C3d/EBV receptor (CR2)

Nunez, Daniele; Charriaut‐Marlangue, Christiane; Barel, Monique; Benveniste, Jacques; Frade, Raymond

doi:10.1002/eji.1830170413

Cited by 37 publications

(14 citation statements)

References 45 publications

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“…One caveat of this assay is that we may be detecting viral nucleic acid within the platelets. Human platelets express C3d complement receptor type II (CR2), a receptor for EBV, suggesting platelets might also be infected by γHV68 [37]. Importantly, murine platelets are not thought to express CR2 [38], making it unlikely γHV68 directly infects them in vivo.…”

Section: Resultsmentioning

confidence: 99%

Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice

Freeman¹,

Burkum²,

Lanzer³

et al. 2013

Journal of Autoimmunity

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Human herpesviruses establish lifelong latency. Viral recrudescence can lead to the development of cancers, immunoproliferative disorders, transplantation complications, and thrombocytopenia. Although platelet-specific autoantibodies have been reported in patients infected with the Epstein-Barr virus (EBV), the mechanisms by which thrombocytopenia is induced remain unclear, as do the relative contributions of lytic viral replication and latent viral gene expression. The human gammaherpesviruses are tightly restricted in their ability to infect other mammals, so they are difficult to study in live animal models. Here we show that infection of mice with murine gammaherpesvirus-68 (γHV68), a rodent-specific pathogen closely related to EBV, induces the production of platelet-binding antibodies and causes thrombocytopenia. Infection of antibody-deficient mice does not lead to thrombocytopenia, indicating the platelet decrease is mediated by antibody. Additionally, infection with a latency-null recombinant γHV68 does not induce thrombocytopenia, suggesting factors associated with viral latency drive the infection-induced antibody-mediated thrombocytopenia. These studies describe an important animal model of gammaherpesvirus-induced autoimmune thrombocytopenia and demonstrate that this pathology is mediated by antibody and dependent on viral latency. This model will allow studies of the underlying mechanisms of disease progression and the testing of therapeutic strategies for the alleviation of virus-induced thrombocytopenia.

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Section: Resultsmentioning

confidence: 99%

Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice

Freeman¹,

Burkum²,

Lanzer³

et al. 2013

Journal of Autoimmunity

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“…6–7), despite being components that are structurally and functionally similar (20). CR2 (CD21; C3d/iC3b receptor) may be a receptor for C3(H 2 O) on B lymphocytes (50), and CR2 has been identified on the surface of platelets (72). It is also possible that the C3a region that is present in C3(H 2 O), but not in C3b, may contain a site important for interacting with activated platelets.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Mode of Complement Activation on Stimulated Platelets Mediated by Properdin and C3(H2O)

Saggu

Cortés

Emch

et al. 2013

The Journal of Immunology

107

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Artículo de publicación ISIElevated numbers of activated platelets circulate in patients with chronic inflammatory diseases, including atherosclerosis and coronary disease. Activated platelets can activate the complement system. Although complement activation is essential for immune responses and removal of spent cells from circulation, it also contributes to inflammation and thrombosis, especially in patients with defective complement regulation. Proinflammatory activated leukocytes, which interact directly with platelets in response to vascular injury, are among the main sources of properdin, a positive regulator of the alternative pathway. The role of properdin in complement activation on stimulated platelets is unknown. Our data show that physiological forms of human properdin bind directly to human platelets after activation by strong agonists in the absence of C3, and bind nonproportionally to surface CD62P expression. Activation of the alternative pathway on activated platelets occurs when properdin is on the surface and recruits C3b or C3(H2O) to form C3b,Bb or a novel cell-bound C3 convertase [C3(H2O),Bb], which normally is present only in the fluid phase. Alternatively, properdin can be recruited by C3(H2O) on the platelet surface, promoting complement activation. Inhibition of factor H–mediated cell surface complement regulation significantly increases complement deposition on activated platelets with surface properdin. Finally, properdin released by activated neutrophils binds to activated platelets. Altogether, these data suggest novel molecular mechanisms for alternative pathway activation on stimulated platelets that may contribute to localization of inflammation at sites of vascular injury and thrombosis

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“…Epstein–Barr virus (EBV) interaction with platelets occurs via complement receptor 2 (CR2) ( 43 ). HIV and dengue virus activate platelets by binding to lectin receptors such as C-type lectin domain family 2 (CLEC-2) and cell-specific intercellular adhesion molecule-3-grapping non-integrin (DC-SIGN) ( 44 ).…”

Section: Enhanced Platelet Destructionmentioning

confidence: 99%

Platelets and Infection â€“ An Emerging Role of Platelets in Viral Infection

2014

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Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis) are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia) and several platelet function disorders increase the risk of bleeding. Over the last years, more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients. Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favors platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen–antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies. All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count but also shape immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation, and platelet-mediated modulations of innate and adaptive immune responses.

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Activation of human platelets through gp140, the C3d/EBV receptor (CR2)

Cited by 37 publications

References 45 publications

Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice

Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice

Identification of a Novel Mode of Complement Activation on Stimulated Platelets Mediated by Properdin and C3(H2O)

Platelets and Infection â€“ An Emerging Role of Platelets in Viral Infection

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