tRNA-derived small RNA, tsRNA-5017b, as a novel biomarker for predicting severity in severe fever with thrombocytopenia syndrome

ABSTRACT tRNA-derived small RNAs (tsRNAs) represent a novel class of highly conserved non-coding RNAs that play crucial roles in various cellular processes, including cell proliferation and the initiation of viral reverse transcription. Despite their significant biological functions, studies exploring the role of tsRNAs in infectious diseases remain limited. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever caused by SFTS virus (SFTSV), which is associated with a high fatality rate. This study investigates the potential diagnostic value of serum tsRNAs in SFTS. Using tsRNA sequencing, we analyzed the differential expression of serum tsRNAs between SFTS patients and healthy controls, followed by validation using quantitative real-time PCR (qRT-PCR) in individual samples. Our findings revealed that the expression levels of tsRNA-3002a, tsRNA-5007a, tsRNA-5013c, tsRNA-5017b, tsRNA-5027b, and tsRNA-5030c were significantly altered in the serum of SFTS patients compared to healthy controls. Among these, tsRNA-5017b showed the most pronounced upregulation, with its expression progressively increasing in parallel with the severity of the disease. Further analysis demonstrated that tsRNA-5017b alone could predict SFTS severity at admission with a specificity of 93%. When combined with conventional laboratory markers such as platelet count (PLT) and aspartate aminotransferase (AST), the sensitivity reached 91.7%. Bioinformatics analysis suggested that tsRNA-5017b may be involved in the regulation of immune responses, apoptosis, and inflammatory pathways. In conclusion, this study is the first to identify the expression of tsRNA in the serum of SFTS patients and proposes tsRNA-5017b as a promising biomarker for predicting disease severity at admission. IMPORTANCE Severe fever with thrombocytopenia syndrome (SFTS) is a fatal tick-borne disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV), with limited early diagnostic tools available. This study identifies serum tRNA-derived small RNAs (tsRNAs) as potential biomarkers for SFTS, revealing that tsRNA-5017b, in particular, correlates with disease severity. Our findings show that tsRNA-5017b is associated with SFTS severity at admission, with high specificity alone and improved sensitivity when combined with conventional markers. This research highlights the potential of tsRNA-based biomarkers in diagnosing and assessing disease severity in SFTS, advancing our understanding of viral pathogenesis and immune regulation in infectious diseases.