Innate Immunity of Platelets: Specific Interactions with Viruses

Thrombocytopenia is a frequent complication of many viral infections (hepatitis C virus, adenoviruses, lentiviruses, etc,), showing that interaction of platelets with viruses is an important pathophysiological phenomenon. Multiple mechanisms arc, involved depending on the nature of the infecting viruses: immunological platelet destruction, inappropriate platelet activation and consumption, or impaired megakaryopoiesis. Viruses bind platelets through various links, specific receptors and identified ligands. A review of the specific interactions of platelets with other types of viruses and of the different receptors involved in these interactions is presented. We also report on a study, performed in our laboratory, of the reciprocal effects between platelets, megakaryocytes (MKs) and human immunodeficiency virus (HIV)-1, trying to understand the consequences Of Such interactions. HIV-1 (and replication-deficient HIV-1, insuring optimal biosecurity) were incubated in vitro with human platelets and MKs. HIV-1 internalization was found within two distinct endocytic. compartments and occurred preferentially in activated platelets: firstly, endocytic vesicles devoid of platelet secretion contained intact and potentially infectious viruses; secondly, viruses with altered structure were enclosed in the platelet surface-connected canalicular system (SCCS) in contact with platelet secretary products. Similar dual compartments were identified in MKs. Images suggesting that virus internalization by platelets also occurs in vivo were occasionally found of platelets from patients with acquired immune deficiency syndrome (AIDS) and thrombocytopenia. Finally, the pathogen receptor DC-SIGN was identified on platelets and MKs and facilitates HIV-1 internalization within platelets. In conclusion, virus particles can be specifically internalized in platelets and MKs where they can be sheltered, or get into contact with secretory products that lead to their destruction, This occurs in activated platelets (able to interact with macrophages), potentially leading to platelet clearance from the circulation and to the transfer of their viral load into target organs, Moreover, and similarly to platelets, MKs are also potentially colonized by intact infectious viruses, and the relationship between this observation and the occurrence of thrombocytopenia needs to be further examined. Finally, the understanding of the close platelet interaction with viruses emphasizes the importance of pursuing research on pathogen inactivation in platelet concentrates. (C) 2008 S. Karger GmbH, Freiburg i.Br.