Translational adaptation of human viruses to the tissues they infect

Xavier Hernandez-Alias; Martin Schaefer; Luis Serrano

Specifically, we therefore focus our analysis on the new SARS-CoV-2 coronavirus, causative of the current COVID-19 pandemic. As has been recently suggested based on the expression of their entry receptor 21, 22 , SARS-CoV-2 is also translationally adapted to the upper respiratory airways, as well as the lung parenchyma. This upper tract tropism has indeed been linked to the higher transmissibility of the strain 21 . The novel coronavirus showcases the highest SDA among all studied coronaviruses, including lung but also other tissues such as the digestive system and brain. Interestingly, recent reports have shown that COVID-19 patients very frequently have problems in the digestive tract 24,46,47 as well as in neural tissue 23 One major open question in the field still persists: how much natural selection before or after zoonosis shapes the current coronavirus 50 . On the one hand, viruses tend to gradually change their codon usage after a zoonotic jump 43, 45 . On the other hand, given the similarity of SARS-CoV-2 SDA with the phylogenetically closest bat coronavirus, it seems that a translational selection to increase SDA would have acted before the putative zoonosis from bats or other intermediate hosts. Furthermore, in agreement with the highest translational potential of SARS-CoV-2 in their target tissues, a recent model of viral tropism suggested that a tradeoff exists between the efficiency of viral translation and the translational load on the host, indicating that an improved codon usage can make the difference between symptomatic and natural hosts 51 .