Atypical Lymphocytes in Lymphoid and Non-Lymphoid Organs were the Major Targets of SFTSV Infection in Humans Tadaki Suzuki1,*, Takeshi Arashiro1, Kaori Sano1, Yuko Sato1, Yuji Wada1, Harutaka Katano1, Noriko Nakajima1, Shigeru Morikawa2, Hideki Hasegawa1, 1Department of Pathology, National Institute of Infectious Diseases; 2Department of Veterinary Science, National Institute of Infectious Diseases
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high case fatality risk caused by the SFTS virus (SFTSV). SFTSV is a tick borne phlebovirus in the family Bunyaviridae that was first isolated in China and reported in 2011. Clinical features of SFTS include high fever, thrombocytopenia, leukocytopenia, and gastrointestinal symptoms with a case fatality rate reported to be about 15% in Japan. These clinical features indicate that some pathological lesions occur in multiple organs including lymphoid organs in SFTS patients. To elucidate pathogenesis of this lethal phlebovirus infection, we performed pathological examination using human pathological specimens obtained from Japanese SFTS cases. The analysis of 24 SFTS cases revealed that the histopathological characteristics of SFTS are necrotizing lymphadenitis and extensive hemophagocytosis, and the major target cells of viral infection are atypical lymphocytes in lymphoid organs such as lymph nodes, spleen and bone marrow. In addition, the non-lymphoid visceral organs also showed abundant viral antigen positive cells. Interestingly, viral antigens were detected exclusively in atypical lymphocytes but not parenchymal cells of these non-lymphoid visceral organs. Furthermore, the viral antigens were also detected in circulating lymphocytes within blood vessels in these non-lymphoid visceral organs. To characterize these viral target atypical lymphocytes in SFTS cases, the double immunofluorescence staining for cellular markers in SFTSV virus positive cells were performed. The analysis showed that the atypical lymphocytes in SFTS are expressing several cell surface proteins commonly appeared in plasmablasts. These observations suggest that the target lymphocytes of SFTSV infection are plasmablasts, and the infected plasmablasts in SFTS cases might play a pivotal role in the pathogenesis of SFTS virus infection.