CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome.

Ample evidence indicates that codon usage bias regulates gene expression. How viruses, such as the emerging mosquito-borne Chikungunya virus (CHIKV), express their genomes at high levels despite an enrichment in rare codons remains a puzzling question. Using ribosome footprinting, we analyze translational changes that occur upon CHIKV infection. We show that CHIKV infection induces codon-specific reprogramming of the host translation machinery to favor the translation of viral RNA genomes over host mRNAs with an otherwise optimal codon usage. This reprogramming was mostly apparent at the endoplasmic reticulum, where CHIKV RNAs show high ribosome occupancy. Mechanistically, it involves CHIKV-induced overexpression of KIAA1456, an enzyme that modifies the wobble U34 position in the anticodon of tRNAs, which is required for proper decoding of codons that are highly enriched in CHIKV RNAs. Our findings demonstrate an unprecedented interplay of viruses with the host tRNA epitranscriptome to adapt the host translation machinery to viral production. Viruses completely depend on the host translational machinery, but their genomes are often enriched in rare codons and therefore should be translated with poor efficiency. Here, Jungfleisch et al. apply Ribo-Seq and RNASeq to provide a global view on the translational changes occurring during Chikungunya virus (CHIKV) infection. CHIKV infection induces a codon-specific reprogramming of the host translation machinery to favor the translation of viral RNA genomes over host mRNAs via tRNA modification. [ABSTRACT FROM AUTHOR]