Translational adaptation of human viruses to the tissues they infect

• Published in: Cell reports (Cambridge) Vol. 34; no. 11; p. 108872
• Main Authors: Hernandez-Alias, Xavier, Benisty, Hannah, Schaefer, Martin H., Serrano, Luis
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.03.2021; The Author(s)
• Subjects: Cell Line; Cell Line, Tumor; codon usage; Codon Usage - genetics; Genes, Neoplasm - genetics; HCT116 Cells; HEK293 Cells; HeLa Cells; Hep G2 Cells; Humans; Protein Biosynthesis - genetics; Pulmonary Alveoli - virology; Respiratory Tract Infections - virology; RNA, Transfer - genetics; SARS-CoV-2; tissue; translation; tRNA; tropism; Tropism - genetics; Viral Proteins - genetics; Virus Diseases - genetics; Virus Diseases - virology; Viruses - genetics; tropism; translation; SARS-CoV-2; tissue; tRNA; codon usage
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.108872

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. [Display omitted] •Viruses with distinct tissue tropisms show differences in codon usage•Viral tropism defines a unique pattern of translational adaptation to human tissues•SARS-CoV-2 is especially favored to the upper respiratory tract and the alveoli•Early viral proteins are generally better adapted than late counterparts Viruses need to hijack the translational machinery of the host for the expression of their own proteins. Hernandez-Alias et al. show that viruses that infect different tissues use different synonymous codons, which can affect the efficiency in which they are translated across human tissues.