Differential Evolution of Antiretroviral Restriction Factors in Pteropid Bats as Revealed by APOBEC3 Gene Complexity

Hayward, Joshua A; Tachedjian, Mary; Cui, Jie; Cheng, Adam Z; Johnson, Adam; Baker, Michelle L; Harris, Reuben S; Wang, Lin-Fa; Tachedjian, Gilda

This study was undertaken to address the question of differential antiviral gene evolution in bats, and more specifically, whether important differences exist in a major class of genes that control and restrict retroviruses and genomic retroelements. We demonstrated that bats possess 18 A3 genes, 13 of which are transcriptionally active in spleen tissue, with several proving active in a heterologous E. coli base mutation assay or MBE an HIV-1 restriction assay. In addition to the expected A3Z1, A3Z2, and A3Z3 phylogenetic subtypes, we identified an additional division within the bat A3Z2 clade in which we designated A3Z2A as the prototypical A3Z2 subtype, and A3Z2B, as a subdivision that possesses a combination of invariant amino residues key to the amino acid character of both the A3Z1 and A3Z2 subtypes. Representative A3 loci have previously been delineated for every Eutherian order with the exceptions of Chiroptera (bats) and all orders within the clade Afrotheria (e.g., elephants, tenrecs, dugongs, and hyraxes) (Nakano et al. 2017) . With the caveat that the A3 loci of the vast majority of mammalian species remain to be resolved, the pteropid bat species studied here are shown to possess the largest and most phylogenetically diverse antiviral A3 gene repertoire of any mammal reported to date.