Translational adaptation of human viruses to the tissues they infect

Xavier Hernandez-Alias; Martin Schaefer; Luis Serrano

Moreover, given that the tropisms not only depend on the translational adaptation to the host, but also on the expression of the required entry receptors, we measure the respective receptors of each virus. Influenza A viruses bind to α(2,6)-linked and α(2,3)-linked sialic acids, which are synthesized by the enzymes ST6GAL1 and ST3GAL4, respectively 34 . While their expression is relatively uniform along the airways, the MERS-CoV uses the parenchymaspecific receptor DPP4 (Fig. 3B) 35 . In both cases, the expression of their entry receptor coincides with an optimal translational adaptation in the lower respiratory tract. On the other hand, both the SARS-CoV and SARS-CoV-2 strains bind to the ACE2 protein and require the proteolytic priming of the viral spike protein by TMPRSS2 36 , although the receptor BSG/CD147 has also been proposed 37 . In all cases, their expression throughout the airways (Fig. 3B ) alongside their efficient translational adaptation defines the upper respiratory tract and the alveoli as their particular optimal tropism (Fig. 3C ). This is in agreement with recent single-cell transcriptomic studies reporting the expression of ACE2 in the nasal goblet and ciliated cells as well as the type-2 alveolar epithelial cells 21, 22 .