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.
journal_name
Bloodjournal_title
Bloodauthors
Koupenova M,Vitseva O,MacKay CR,Beaulieu LM,Benjamin EJ,Mick E,Kurt-Jones EA,Ravid K,Freedman JEdoi
10.1182/blood-2013-11-536003subject
Has Abstractpub_date
2014-07-31 00:00:00pages
791-802issue
5eissn
0006-4971issn
1528-0020pii
blood-2013-11-536003journal_volume
124pub_type
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