Bats Possess Unique Variants of the Antiviral Restriction Factor Tetherin

Joshua A. Hayward; Mary Tachedjian; Adam Johnson; Tamsin B. Gordon; Jie Cui; Glenn A. Marsh; Michelle L. Baker; Lin-Fa Wang; Gilda Tachedjian

Bat tetherin amino acid sequences were found to be highly variable. The predicted protein lengths range from 177 to 221 AA (human l-tetherin is 180 AA) and of these, only 23 amino acid residues were found to be conserved in 100% of the 27 bat tetherin sequences analysed ( Figure 1B ). Among these are the structurally important cysteine and asparagine residues which are responsible for tetherin dimerisation and glycosylation, respectively (45, 46) . The dual-tyrosine motif, responsible for mediating viral particle endocytosis and immune signaling (25, 34) , was found to exist as a variable Y|C·x·Y|H . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.08.031203 doi: bioRxiv preprint motif across the bat tetherin variants analysed. All bats maintained at least one of the two tyrosine residues. This observation is significant because mutational studies of human tetherin have demonstrated that the dual tyrosines provide redundancy for both the endocytic and signaling activities, which are maintained so long as either tyrosine is present (25, 34).