Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne
infectious disease caused by the SFTS virus (SFTSV) and with a high fatality rate.
Thrombocytopenia is a major clinical manifestation observed in SFTS patients, but the underlying mechanism remains largely unclear. Here, we explored the effects of SFTSV
infection on platelet function in vivo in severely infected SFTSV IFNar-/- mice and on mouse and human platelet function in vitro. Results showed that SFTSV-induced platelet clearance acceleration may be the main reason for
thrombocytopenia. SFTSV-potentiated platelet activation and apoptosis were also observed in infected mice. Further investigation showed that SFTSV
infection induced platelet
reactive oxygen species (ROS) production and
mitochondrial dysfunction. In vitro experiments revealed that administration of SFTSV or SFTSV
glycoprotein (Gn) increased activation, apoptosis, ROS production, and
mitochondrial dysfunction in separated mouse platelets, which could be effectively ameliorated by the application of
antioxidants (NAC (
N-acetyl-l-cysteine), SKQ1 (10-(6'-plastoquinonyl)
decyltriphenylphosphonium) and
resveratrol). In vivo experiments showed that the
antioxidants partially rescued SFTSV
infection-induced
thrombocytopenia by improving excessive ROS production and
mitochondrial dysfunction and down-regulating platelet apoptosis and activation. Furthermore, while SFTSV and Gn directly potentiated human platelet activation, it was completely abolished by
antioxidants. This study revealed that SFTSV and Gn can directly trigger platelet activation and apoptosis in an ROS-MAPK-dependent manner, which may contribute to
thrombocytopenia and
hemorrhage during
infection, but can be abolished by
antioxidants.