Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in a non-human primate model (P3021)

Severe Fever with Thrombocytopenia Syndrome (SFTS) emerged as an infectious disease in 2010 in rural China, and its causative agent SFTS virus (SFTSV) is a new member of the family Bunyaviridae, genus phlebovirus, most closely related to the heartland virus recently discovered in Missouri, the US. To develop effective vaccines and therapeutics against this emerging pathogen, animal disease models are urgently needed. Here, we report the first findings of measurable clinical disease in non-human primates infected with SFTSV. In the primate model, the abrupt fever, thrombocytopenia, and leukocytopenia were duplicated. Substantially enhanced aspartate aminotransferase, creatinine, and lactate dehydrogenase in serum was observed, indicating pathological lesions in organs. Viremia peaked around 3 to 5 days after the inoculation of SFTSV. Viral RNA was detected in the spleen, lymph node, liver, kidney, and intestine. Virus-specific IgM and IgG antibody responses were induced, and cytokines IFN-γ and eotaxin were significantly enhanced in the acute phase. Scattered necrosis and degeneration of hepatocytes in liver, as well as glomerular hypercellularity, mesangial thickening, and congestion in Bowman’s space in kidney were observed after 4 weeks of SFTSV infection. Thus, we established a non-human primate model which resembles major clinical features of the human SFTS disease, and further studied virus-specific immune responses and histopathological changes in this primate model.