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: 9.67). 06/2012; 109(25):10053-8. DOI: 10.1073/pnas.1120246109
Source: PubMed


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.

Download full-text


Available from: Mifang F Liang
  • Source
    • "The comparably milder disease in pediatric patients therefore might be derived from the host factor. Jin et al. have demonstrated that virus replication and overexuberant immune responses can contribute to progressive organ damage [9]. Moreover, dramatically elevated proinflammatory cytokine levels have been detected in severe or fatally infected patients, suggestive of a cytokine storm might contribute to the adverse disease outcome [10-12]. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Jul 2014 · BMC Infectious Diseases
  • Source
    • "Her hemoglobin (Hb) and red blood cell (RBC) counts remained stable throughout her illness, consistent with the absence of any hemorrhagic complications from her thrombocytopenia and coagulation disorder. Late in the disease SFTSV can invade the heart, liver, kidney, gastrointestinal tract, and other vital organs, as well as the bloodstream [16]; our case was not tested for focal organ involvement. In the case reported here, kidney and liver dysfunction became more evident, as indicated by the elevated BUN, creatinine and liver transaminases. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper describes the first case of infection with a recently described novel bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), in Shanghai, China. The case is originally from Chizhou City, Anhui province within an endemic area for SFTSV. We describe the etiology, epidemiological characteristics, clinical diagnosis and treatment of this fatal case. This case is unique because major cause of death was renal failure, whereas other reported cases have been due to hemorrhage. The investigation and response to this case provides meaningful insight for the early and rapid diagnosis, treatment, prevention and control of severe fever with thrombocytopenia syndrome virus in non-endemic regions in China and globally.
    Full-text · Article · Jun 2013 · Virology Journal
  • Source
    • "In this murine model, viral RNA was detected in the blood, spleen, liver, and kidney. The humoral immune responses of virus-specific IgM and IgG, neutralizing antibodies, and cellular responses were efficiently induced in the SFTSV-infected mice.21 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was discovered in China in 2010. The causative agent has been identified as a new member of the Phlebovirus genus in the family Bunyaviridae and has been designated severe fever with thrombocytopenia virus (SFTSV). SFTSV infection can be transmitted person-to-person, and the average case fatality rate is approximately 10% in humans. There is a high seroprevalence of SFTSV infection in a wide range of domesticated animals, including sheep, goats, cattle, pigs, dogs and chickens. Ticks are suspected to be the vector that transmits the virus to humans. Currently, the SFTS endemic area is expanding. Therefore, SFTSV infection is an increasingly important public health threat.
    Full-text · Article · Jan 2013 · Emerging Microbes and Infections
Show more