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

We amplified tetherin from spleen-derived cDNA of the Australian fruit bat, P. alecto, and confirmed the expression of the two computationally predicted splice variants (isoforms A [X1] and B [X2]), and additionally identified the expression of a third isoform of tetherin, isoform C. Mapped against the P. alecto genome, all three isoforms were found to be derived from the alternative splicing of a single tetherin gene ( Figure 3B ). P. alecto tetherin isoform B was found to possess a 7 AA exclusion within the extracellular coiledcoil domain relative to isoform A, while isoform C is predicted to harbor the same 7 AA exclusion and an alternative C-terminus, that lacks the GSP predicted to be present in tetherin isoforms A and B which is necessary for the post-translational addition of the GPI-anchor. This is important because studies of human tetherin have demonstrated that . 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 the presence of a GPI-anchor is essential for restricting the release of viral particles (22, 36) . Sheep and cows have been reported to possess a duplication of the tetherin gene (35, 43) . In sheep, the duplicate tetherin, named tetherin B, similarly does not encode a GSP, and studies of sheep tetherin B function reveal that while it is capable of limited restriction of VLPs, it is significantly less potent than sheep tetherin A (43) . The mechanism of its function is unknown and its C-terminal amino acid sequence is entirely dissimilar from that of P. alecto tetherin isoform C. One possible function of additional isoforms of tetherin is to expand the viral target range of bats by undefined mechanisms that are active in the absence of a GPI anchor.