Oral Presentation 9th Australasian Virology Society Meeting 2017

Differential evolution of antiviral immunity in bats as revealed by apobec3 gene complexity (#8)

Joshua A Hayward 1 , Mary Tachedjian 2 , Jie Cui 3 , Adam Cheng 4 5 , Adam Johnson 1 , Michelle Baker 2 , Reuben Harris 4 5 , Linfa Wang 6 , Gilda Tachedjian 1
  1. Retroviral Biology and Antivirals Laboratory, Life Sciences Discipline, Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia
  2. Animal, Food and Health Sciences, Australian Animal Health Laboratory, CSIRO, Geelong, VIC, Australia
  3. Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China
  4. Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
  5. Howard Hughes Medical Institute, University of Minnesota, Minneapolis, Minnesota, USA
  6. Emerging Infectious Disease Program, Duke-NUS Graduate Medical School, Singapore

Background:

Bats have attracted attention in recent years as significant reservoirs of viruses deadly to humans and other mammals. These infections typically produce no clinical symptoms of disease in bats raising questions about what innate immune differences might exist between bats and other mammals. The APOBEC3 gene family encodes antiviral DNA cytosine deaminases, which are restriction factors with important roles in the suppression of diverse viruses and genomic parasites.

Results:

Here we characterize the megabat (family Pteropodidae) APOBEC3 genes and show that pteropid bats possess the largest and most diverse array of APOBEC3 genes identified in any mammal reported to date. Several bat APOBEC3 proteins are demonstrated to be capable of restricting retroviral infectivity using HIV-1 as a model, and A3Z1 subtypes demonstrate strong DNA deaminase activity. Hypermutation analysis of the endogenous retroviruses of P. vampyrus supports a role for APOBEC3-mediated restriction of ancient bat retroviruses, and a molecular clock analysis indicates that the expansion of APOBEC3 genes coincides with the extinction of pteropid LINE-1 retroelements.

Conclusion:

These findings reveal the first group of antiviral restriction factors identified in bats with extensive diversification and divergence relative to homologues of other mammals.