tRNA-derived fragments restrict KSHV lytic replication through miRNA-like repression of host pro-viral signalling networks

Host tRNA-derived fragments are dynamically reprogrammed during Kaposi sarcoma-associated herpesvirus (KSHV) lytic replication, with tRF-His-GTG, tRF-Gly-CCC, and tRF-Lys-CTT robustly induced and antiviral.

• Why it matters: The roles of tRFs in virus infection are poorly understood, despite evidence they regulate gene expression in other contexts.
• What they did: Transcriptome-wide profiling after viral reactivation identified induced tRFs independent of parental tRNA abundance, and functional assays showed suppression of viral gene expression and infectious virion production.
• The result: tRF-His-GTG and tRF-Lys-CTT associate with AGO2 complexes to mediate sequence-specific repression of host targets, including SHF, which promotes PI3K/Akt signalling, cellular survival, and efficient viral replication.