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.

大量证据表明密码子使用偏差调节基因表达。尽管富含稀有密码子，病毒（例如新兴的蚊媒基孔肯雅病毒 (CHIKV)）如何以高水平表达其基因组仍然是一个令人费解的问题。使用核糖体足迹，我们分析了 CHIKV 感染后发生的平移变化。我们表明，CHIKV 感染诱导宿主翻译机器的密码子特异性重编程，以有利于病毒 RNA 基因组的翻译，而不是宿主 mRNA，否则密码子使用最佳。这种重编程在内质网中最为明显，在那里 CHIKV RNA 显示出高核糖体占有率。从机制上讲，它涉及 CHIKV 诱导的 KIAA1456 过表达，KIAA1456 是一种修饰 tRNA 反密码子中 U34 摆动位置的酶，这是正确解码在 CHIKV RNA 中高度富集的密码子所必需的。我们的研究结果证明了病毒与宿主 tRNA 表观转录组的前所未有的相互作用，以使宿主翻译机制适应病毒生产。