Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model.
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.
Laboratory of Viral Hemorrhagic Fever,  National Institute for Viral Disease Control and Prevention, China Center for Disease Control Beijing 102206,  China.
Cong
C
Jin
Mifang
M
Liang
Junyu
J
Ning
Wen
W
Gu
Hong
H
Jiang
Wei
W
Wu
Fushun
F
Zhang
Chuan
C
Li
Quanfu
Q
Zhang
Hua
H
Zhu
Ting
T
Chen
Ying
Y
Han
Weilun
W
Zhang
Shuo
S
Zhang
Qin
Q
Wang
Lina
L
Sun
Qinzhi
Q
Liu
Jiandong
J
Li
Tao
T
Wang
Qiang
Q
Wei
Shiwen
S
Wang
Ying
Y
Deng
Chuan
C
Qin
Dexin
D
Li
D000818:Animals; D001792:Blood Platelets / Q000276:immunology; D002448:Cell Adhesion; D004195:Disease Models, Animal; D005334:Fever / Q000209:etiology / Q000473:pathology / Q000821:virology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D012367:RNA, Viral / Q000235:genetics; D013921:Thrombocytopenia / Q000150:complications / Q000473:pathology / Q000821:virology*; D014777:Virus Diseases / Q000150:complications / Q000473:pathology / Q000821:virology*
D012367:RNA, Viral