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

These microbats were found to express various homologs of tetherin that include encoding of unique structural variations ( Figure 4A and 4B). The tetherin homolog of human l-tetherin predicted for M. schreibersii was detected ( Figure 4A ). Five unique tetherin variants, differing in their encoded primary amino acid sequences (tetherin A -E), were identified for M. macropus, two of which, tetherin A and B, were also detected in M. ricketti ( Figure 4A ). These tetherin variants encode three distinct homologs (tetherin A, C, D) of the human l-tetherin, sharing the same protein domains and secondary structures but differing in their primary amino acid sequence ( Figure 4B The copyright holder for this preprint (which was not peer-reviewed) is the .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 extracellular domain ( Figure 4B ). Accordingly, it is predicted to lack the GPI signal peptide required for the post-translational addition of a GPI-anchor, also found for P. alecto tetherin isoform C ( Figure 2B ). The absence of a GPI anchor indicates that it is unlikely that homodimers of M. macropus tetherin C isoform B would possess the capacity to tether viral particles to the cell. M. macropus tetherin B and E were found to be structurally unique, possessing a large deletion of ~60 amino acids in the extracellular coiled-coil domain ( Figure 4B ), compared to the other tetherin homologs, which has been shown to be critical for viral particle restriction (22, 36) . This deletion results in the exclusion of the conserved disulphide bond-forming cysteine residues, and the conserved asparagine-linked glycosylation sites, indicating that this form of tetherin is unlikely to form dimers or be glycosylated in the manner of human tetherin (22, 37) . Figure 6A ) and