title: Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis.
abstract: Viral infections have been associated with reduced platelet counts, the biological significance of which has remained elusive. Here, we show that infection with encephalomyocarditis virus (EMCV) rapidly reduces platelet count, and this response is attributed to platelet Toll-like receptor 7 (TLR7). Platelet-TLR7 stimulation mediates formation of large platelet-neutrophil aggregates, both in mouse and human blood. Intriguingly, this process results in internalization of platelet CD41-fragments by neutrophils, as assessed biochemically and visualized by microscopy, with no influence on platelet prothrombotic properties. The mechanism includes TLR7-mediated platelet granule release, translocation of P-selectin to the cell surface, and a consequent increase in platelet-neutrophil adhesion. Viral infection of platelet-depleted mice also led to increased mortality. Transfusion of wild-type, TLR7-expressing platelets into TLR7-deficient mice caused a drop in platelet count and increased survival post EMCV infection. Thus, this study identifies a new link between platelets and their response to single-stranded RNA viruses that involves activation of TLR7. Finally, platelet-TLR7 stimulation is independent of thrombosis and has implications to the host immune response and survival.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA; Department of Medicine, and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA;
authors.forename: Milka
authors.initials: M
authors.lastname: Koupenova
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA;
authors.forename: Olga
authors.initials: O
authors.lastname: Vitseva
authors.affiliation: Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA;
authors.forename: Christopher R
authors.initials: CR
authors.lastname: MacKay
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA;
authors.forename: Lea M
authors.initials: LM
authors.lastname: Beaulieu
authors.affiliation: Department of Medicine, and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA; National Heart, Lung, and Blood Institute and Boston University's Framingham Heart Institute, Framingham, MA;
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: Division of Quantitative Health Sciences, Department of Medicine, University of Massachusetts Medical School, Worcester, MA; and.
authors.forename: Eric
authors.initials: E
authors.lastname: Mick
authors.affiliation: Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA;
authors.forename: Evelyn A
authors.initials: EA
authors.lastname: Kurt-Jones
authors.affiliation: Department of Medicine, and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA; Evans Center for Interdisciplinary Biomedical Research, Boston University School of Medicine, Boston, MA.
authors.forename: Katya
authors.initials: K
authors.lastname: Ravid
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA;
authors.forename: Jane E
authors.initials: JE
authors.lastname: Freedman
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D018188:Cardiovirus Infections / Q000097:blood / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology; D004686:Encephalomyocarditis virus / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010976:Platelet Count; D022142:Secretory Vesicles / Q000276:immunology / Q000378:metabolism; D013927:Thrombosis; D051199:Toll-Like Receptor 7 / Q000097:blood / Q000276:immunology*
chemical_list: D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; C495348:TLR7 protein, human; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7
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