Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever disease caused by the SFTS virus (SFTSV). Despite pandemic concerns arising from repeated instances of human-to-human transmission and a high fatality rate, effective anti-SFTSV interventions remain unavailable. Here, utilizing single-cell RNA sequencing (scRNA-seq) and flow cytometry data, we revealed that the deficiency and dysfunction states of T cells, particularly the impaired cytotoxicity and exhausted state of CD4+ T cells, were significantly associated with lethal consequences in SFTS patients. Using an infectious mouse model, we further observed that depletion of CD4+ T and CD8+ T cells was related to elevated viremia and increased fatality rates in SFTSV-infected mice. Accordingly, we designed virus envelope glycoprotein-targeting bispecific T cell engager (BiTE) antibodies to redirect T cells to eliminate SFTSV-infected cells, effectively rescuing mice from lethal SFTSV infection. Collectively, Gn-targeted BiTEs hold potential as a therapeutic option for treating SFTS.