Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model.

Laboratory of Viral Hemorrhagic Fever, National Institute for Viral Disease Control and Prevention, China Center for Disease Control Beijing 102206, China.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 06/2012; 109(25):10053-8. DOI: 10.1073/pnas.1120246109
Source: PubMed

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.

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    ABSTRACT: Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus (SFTSV) in China. Humans of all ages living in endemic areas have high risk of acquiring SFTS. Most clinical data so far have been from adults and no clinical study was available from children yet. The present study identified four SFTSV infected children through hospital based surveillance. A prospective observational study was performed to obtain their clinical and laboratory characteristics. Case presentation The patients’ age ranged from 4–15 years old and two were male. On hospitalization, fever, malaise and gastrointestinal syndromes were the most commonly presenting symptoms. Hemorrhagic symptoms or neurological manifestation was not recorded in any of the four pediatric patients. Hematological abnormalities at admission into hospital included leucopenia (4 cases), thrombocytopenia (1 case) and bicytopenia (1 case). The abnormal parameters included elevated aminotransferase (1 case), alanine transaminase (2 case), and lactate dehydrogenase (3 case). Laboratory parameters indicative of renal damage was not observed during the hospitalization. All the patients recovered well without sequelae being observed. Conclusion Compared with adults, pediatric patients with SFTSV infection seem to have less vague subjective complaints and less aggressive clinical course. Thrombocytopenia is suggested to be used less rigorously in recognizing SFTSV infection in pediatric patients, especially at early phase of disease.
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