Thrombocytopenia in Severe Fever with Thrombocytopenia Syndrome Due to Platelets with Altered Function Undergoing Cell Death Pathways

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an important tick borne viral disease in East Asia. An important clinical manifestation of SFTS is thrombocytopenia. To understand the mechanism by which SFTS virus causes thrombocytopenia, platelets from surviving and fatal human cases, as well as from a C57/BL6 mice model were analyzed. Platelet alterations were assessed through RNA transcriptome profiling, ELISA, flow cytometry and quantitative RT-PCR. In humans transcriptome analysis showed that platelets upregulated genes related to type 1 interferon signaling and neutrophil activation. These changes were more significant in survivors than fatal cases. Immunoassays demonstrated increased levels of platelet activation marker CD62P and platelet–neutrophil aggregates. This occur because platelets activate neutrophils to form extracellular traps which capture the virus but result in massive platelets destruction. Platelets underwent multiple death pathways, most notably pyroptosis. In contrast while mice had thrombocytopenia there was no detection of platelet activation or viral proteins in platelets. Instead of widespread death, mice platelets triggered adaptive immunity which led to clearance of viremia through antibodies. 
(SWM)