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

To understand the evolutionary selective pressures on tetherin genes across bat species, a selection test was performed that revealed that bat tetherin genes are under strong positive selection with amino acid positions in and around the transmembrane domain being the region under the strongest selective pressure (Table 2 and Figure 1A ). This is in agreement with previous reports that primate tetherin possess multiple sites under positive selection in this same region (47) . The driver of positive selection in the case of primate tetherin is antagonism by viral counter-measures including HIV-1 Vpu (47). Venkatesh et al. (48) demonstrated that the configuration that tetherin dimers adopt during viral particle retention primarily consists of the GPI-anchor being embedded in the viral envelope and the transmembrane domain remaining attached to the cellular membrane. If this paradigm holds true for bat tetherin, then it follows that the tetherincell membrane interface is the major site of tetherin antagonism in bats and it would be reasonable to speculate that the drivers of this selection are viral antagonists analogous in the mode of interaction, if not structure or function, to lentiviral tetherin antagonists.