Molecular signatures of inflammatory profile and B-cell function in SFTS patients

Severe fever with thrombocytopenia syndrome banyangvirus (SFTSV) induces immunopathogenic disease with high fatality rate. Despite serious health concern, the mechanisms underlying clinical manifestations are largely unknown. Here, we applied targeted proteomics and single-cell transcriptomics analyses to examine the differential immune landscape of SFTS patient blood. Serum immunoprofiling distinguished Low-risk and High-risk clusters of SFTS patients with differential inflammatory cytokine levels, which matched with disease severity. Single-cell transcriptomics analysis of SFTS patient blood at different infection state showed pronounced expansion of B cells with the alteration of B-cell subset populations, specifically in fatal patients. Furthermore, plasma cells were the primary reservoir of SFTSV replication with the downregulation of IFN pathway. This study identifies not only the molecular signatures of serum inflammatory profile and B cell lineage population, but also plasma cells as the viral reservoir in SFTSV-induced fatal patients, suggesting the alteration of B cell function linked to SFTS lethal infection. PBMC from Control, Infection, Recovery and Fatal SFTS patients were collected in hospitals throughout South Korea. PBMC from each individual were processed separately through the ChromiumTM Single Cell Platform with the 10X Genomics ChromiumTM Single Cell 3’ Library and Gel Bead Kit v2 and the Chromium Single Cell A Chip Kit using the standard manufacturer’s protocol.