Severe fever with thrombocytopenia syndrome virus infection induces thymic atrophy in IFNAR-/- mice.

Severe fever with thrombocytopenia syndrome virus (SFTSV) causes severe disease in humans, yet the pathogenesis remains poorly understood. A hallmark of fatal SFTS cases is the marked depletion of T cells. Previous studies on T cell depletion have predominantly focused on alterations in blood and peripheral lymphoid organs, while the thymus, a critical site for T cell development, has remained largely overlooked. In this study, we employed a lethal murine infection model to investigate the impact of SFTSV on thymic function. Our results revealed that SFTSV infected the thymus and induced severe cortical atrophy in type I interferon receptor-deficient (IFNAR-/-) mice, characterized by a dramatic depletion of CD4+CD8+ double-positive (DP) thymocytes. Transcriptomic analysis indicated that thymic damage is likely attributable to impaired thymocyte proliferation and increased apoptosis, which may be a consequence of SFTSV-induced alterations in the thymic microenvironment. We found SFTSV-infected macrophages and dendritic cells in the thymus, which accumulated in the cortex and exhibited elevated secretion of IFN-γ, a cytokine commonly associated with acute thymic atrophy. These results demonstrate thymic atrophy caused by SFTSV infection and suggest potential therapeutic strategies for restoring thymic function and promoting T cell reconstitution.