Bats have attracted attention in recent years as important reservoirs of viruses deadly to humans and other mammals. These infections are typically nonpathogenic in bats raising questions about innate immune differences that might exist between bats and othermammals. The APOBEC3 gene family encodes antiviral DNA cytosine deaminases with important roles in the suppression of diverse viruses and genomic parasites. Here, we characterize pteropid APOBEC3 genes and show that species within the genus Pteropus possess the largest and most diverse array of APOBEC3 genes identified in any mammal reported to date. Several bat APOBEC3 proteins are antiviral as demonstrated by restriction of retroviral infectivity using HIV-1 as a model, and recombinant A3Z1 subtypes possess strong DNA deaminase activity. These genes represent the first group of antiviral restriction factors identified in bats with extensive diversification relative to homologues in other mammals.
Bibliographical noteFunding Information:
This study was supported by Perpetual Trustees (AR/00255 to G.T. and L.-F.W.), the Australian Postgraduate Award and the Monash University Vice Chancellor’s Honours-PhD scholarship (to J.A.H.), the National Health and Medical Research Council Senior Research Fellowship (APP1117748 to G.T.), the National Research Foundation-Competitive Research Programme (NRF2012NRF-CRP001-056 to L.-F.W.), and the National Institute of Health and National Institute of Allergy and Infectious Diseases (R37AI064046 to R.S.H.). R.S.H. is an Investigator of the Howard Hughes Medical Institute and J.C. is supported by National Natural Science Foundation of China (31671324) and CAS Pioneer Hundred Talents Program. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program by the Burnet Institute. The pteropid A3 loci and cDNA sequences have been deposited in GenBank and are listed in supplementary table S2, Supplementary Material online.
- Antiviral immunity
- Restriction factors