Human small non-coding tRNA-derived fragments as key hallmarks of host-virus interaction in viral infections

Viral infections cause deep changes in the host transcriptome, triggering a complex antiviral immune response that involves multiple proteins and molecular and cellular signaling pathways. Traditionally, Transfer RNAs (tRNAs) have been identified for their vital role in protein synthesis, and recent investigations have determined different small non-coding RNAs (sncRNAs), such as transfer RNA-derived small RNAs (tsRNAs), such as tRNA-derived fragments (tRFs), and tRNA-derived stress-induced RNAs (tiRNAs), that also known as a new class of regulatory molecules with crucial roles during viral infection. Current evidence reveals that tsRNAs play key functions at the host–pathogen interface, controlling viral infection through various antiviral mechanisms, including gene silencing, epigenetic regulation, as well as transcriptional and post-transcriptional control. Moreover, the differential expression of tsRNAs has promise for their application as prognostic and diagnostic biomarkers in viral diseases. This review explores current insights into the roles of tsRNAs in viral infections, highlighting their involvement in host-virus interactions. Further, we will be discussing the broader implications of tsRNAs by emphasizing the importance of understanding their diverse regulatory functions in biological processes and human diseases to advance their potential as biomarkers and personalized therapeutic markers.