Translational adaptation of human viruses to the tissues they infect

Xavier Hernandez-Alias; Martin Schaefer; Luis Serrano

Viruses strongly depend on the translational machinery of the host for the expression of their own proteins and, ultimately, their replication. For instance, given the small size of most viral genomes, no or very few tRNA genes are generally autonomously encoded 5 . In terms of codon usage, it has indeed been shown that bacteriophages are specifically adapted to their microbial hosts 6, 7 . This information has been applied in the prediction of viral hosts from metagenomics data 8, 9 . The codon usage of human-infecting viruses is similarly adapted to the host 10, 11 , and actually the concept of codon deoptimization has been applied in the design of attenuated vaccines 12 . leading to changes in their respective translational efficiency 2, 14 . In agreement with this observation, the codon usage of papillomavirus capsid proteins is adapted to the tRNAs of differentiated keratinocytes, where their translation becomes specifically efficient 15, 16 . In addition, upon HIV-1 infection, the host tRNA pool is reprogrammed to favor translation of late viral genes 17 , a phenomenon that is indeed exploited by host antiviral mechanisms 18 . Furthermore, some viruses with a specific tissue tropism resemble the codon bias of highly expressed proteins of their respective infecting tissues 19 . Nevertheless, despite the few aforementioned studies, a high-throughput analysis of the translational selection of viral genomes to their tissue tropism has been heretofore hindered by the absence of tissue-wide tRNA expression data.