Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model
Open Access
- 4 June 2012
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (25), 10053-10058
- https://doi.org/10.1073/pnas.1120246109
Abstract
The discovery of an emerging viral disease, severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), has prompted the need to understand pathogenesis of SFTSV. We are unique in establishing an infectious model of SFTS in C57/BL6 mice, resulting in hallmark symptoms of thrombocytopenia and leukocytopenia. Viral RNA and histopathological changes were identified in the spleen, liver, and kidney. However, viral replication was only found in the spleen, which suggested the spleen to be the principle target organ of SFTSV. Moreover, the number of macrophages and platelets were largely increased in the spleen, and SFTSV colocalized with platelets in cytoplasm of macrophages in the red pulp of the spleen. In vitro cellular assays further revealed that SFTSV adhered to mouse platelets and facilitated the phagocytosis of platelets by mouse primary macrophages, which in combination with in vivo findings, suggests that SFTSV-induced thrombocytopenia is caused by clearance of circulating virus-bound platelets by splenic macrophages. Thus, this study has elucidated the pathogenic mechanisms of thrombocytopenia in a mouse model resembling human SFTS disease.Keywords
This publication has 31 references indexed in Scilit:
- Person-to-Person Transmission of Severe Fever With Thrombocytopenia Syndrome Bunyavirus Through Blood ContactClinical Infectious Diseases, 2012
- Host genetic variation in susceptibility to Punta Toro virusVirus Research, 2011
- Fever with Thrombocytopenia Associated with a Novel Bunyavirus in ChinaNew England Journal of Medicine, 2011
- A New Mouse Model Reveals a Critical Role for Host Innate Immunity in Resistance to Rift Valley FeverThe Journal of Immunology, 2010
- Pathogenic Hantaviruses Direct the Adherence of Quiescent Platelets to Infected Endothelial CellsJournal of Virology, 2010
- Enhanced Histopathology of the SpleenToxicologic Pathology, 2006
- Platelet binding and phagocytosis by macrophagesTransfusion, 2006
- The haemotoxicity of mitomycin in a repeat dose study in the female CD‐1 mouseInternational Journal of Experimental Pathology, 2005
- The Clearance Mechanism of Chilled Blood PlateletsCell, 2003
- Platelet dysfunction contributes to the haemostatic defect in haemorrhagic fever with renal syndromeTransactions of the Royal Society of Tropical Medicine and Hygiene, 1991