Abstract
Bats are recognised as important reservoirs of viruses deadly to other mammals, including humans. These infections are typically nonpathogenic in bats raising questions about host response differences that might exist between bats and other mammals. Tetherin is a restriction factor which inhibits the release of a diverse range of viruses from host cells, including retroviruses, coronaviruses, filoviruses, and paramyxoviruses, some of which are deadly to humans and transmitted by bats. Here we characterise the tetherin genes from 27 species of bats, revealing that they have evolved under strong selective pressure, and that fruit bats and vesper bats express unique structural variants of the tetherin protein. Tetherin was widely and variably expressed across fruit bat tissue-types and upregulated in spleen tissue when stimulated with Toll-like receptor agonists. The expression of two computationally predicted splice isoforms of fruit bat tetherin was verified. We identified an additional third unique splice isoform which includes a C-terminal region that is not homologous to known mammalian tetherin variants but was functionally capable of restricting the release of filoviral particles. We also report that vesper bats possess and express at least five tetherin genes, including structural variants, a greater number than any other mammal reported to date. These findings support the hypothesis of differential antiviral gene evolution in bats relative to other mammals.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
New data has been added to this revision, including: (i) Functional analysis of bat tetherin against filoviral VLPs; (ii) Analysis of the expression of tetherin across various tissues of Pteropus alecto; (iii) Analysis of tetherin expression in P. alecto following treatment with toll-like receptor agonists; and (iv) Analysis of expression of alternate isoforms of P. alecto tetherin. Additional changes have been made to the main text in each section in line with the inclusion of the new data. Additional authors involved in generating the newly added data have been included.