RNA-centered regulation in SFTSV infection: mechanisms, host interactions, and translational implications

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that causes substantial morbidity and high case fatality in severe cases, representing a major public health concern in East Asia. Although protein-mediated mechanisms of SFTSV replication and immune evasion have been extensively studied, accumulating evidence indicates that viral infection is also influenced by RNA-centered regulatory processes. These processes include viral RNA transcription and replication, epitranscriptomic modification, host RNA-binding proteins, RNA interference-related pathways, small RNA responses, and NSs-driven inclusion bodies. Current evidence is strongest for L protein-mediated viral RNA transcription and replication, m⁶A-related regulation of viral RNA stability and translation, selected host RNA-binding proteins involved in viral RNA metabolism, and NSs-mediated antagonism of AGO2-dependent RNA interference and antiviral signaling. In contrast, the direct role of m⁶A in innate immune sensing, the functional significance of virus-derived microRNA-like small RNAs, and the physical protection of viral RNA within NSs-driven condensates remain incompletely established. In this review, we summarize current knowledge of how RNA-centered mechanisms regulate SFTSV RNA fate, viral replication, host adaptation, immune antagonism, and cross-host transmission. We further discuss their potential implications for biomarker discovery and antiviral development, while emphasizing the uneven strength of evidence and the mechanistic and translational barriers that remain. An evidence-stratified RNA-centered framework may help prioritize future studies and guide the rational exploration of RNA-based diagnostic and therapeutic strategies for SFTSV infection.