Translational adaptation of human viruses to the tissues they infect

Viruses need to hijack the translational machinery of the host cell for a productive infection to happen. However, given the dynamic landscape of tRNA pools among tissues, it is unclear whether different viruses infecting different tissues have adapted their codon usage toward their tropism. Here, we collect the coding sequences of 502 human-infecting viruses and determine that tropism explains changes in codon usage. Using the tRNA abundances across 23 human tissues from The Cancer Genome Atlas (TCGA), we build an in silico model of translational efficiency that validates the correspondence of the viral codon usage with the translational machinery of their tropism. For instance, we detect that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is specifically adapted to the upper respiratory tract and alveoli. Furthermore, this correspondence is specifically defined in early viral proteins. The observed tissue-specific translational efficiency could be useful for the development of antiviral therapies and vaccines.We acknowledge the support of the Spanish Ministry of Science and Innovation (MICINN) (PGC2018-101271-B-I00 Plan Estatal), “Centro de Excelencia Severo Ochoa,” the CERCA Programme/Generalitat de Catalunya, and the Spanish Ministry of Science and Innovation (MICINN) to the EMBL partnership. The work of X.H.-A. has been supported by a PhD fellowship from the Fundación Ramón Arece