Hannah Mahoney, University of Saskatchewan

Hannah Mahoney1, Briallen Lobb2, Andrew Doxey2, Linfa Wang3, Vikram Misra4, Arinjay Banerjee1,2,4,5,6 1Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Canada, 2 2Department of Biology, University of Waterloo, Waterloo, Canada. 3Programme in Emerging Infectious Disease, Duke-NUS Medical School, Singapore. 4Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, Canada. 5Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada 6Department of Biochemistry and Molecular Biology, University of British Columbia, BC, Canada.

Suppressing & Conquering

Bats are recognized as reservoir hosts for a diversity of viruses, yet the mechanisms that enable viral persistence without overt disease remain incompletely understood, particularly for DNA viruses. Eptesipox virus is the single member of the Vespertilionpoxvirus family, a novel pox virus isolated from microcheroptan Epetsicus fuscus bats. Here, we investigate host–virus interaction using Eptesicus fuscus cells (Efk3b), Pteropus alecto cells (PaKiT03) and human cells (RPTEC, A549) upon infection with Eptesipox virus (EFPV) as a tractable model to study viral replication, innate immune control, and host tolerance. We broadly hypothesized that bats have evolved both canonical and non-canonical antiviral mechanisms to tolerate infection with bat-derived DNA viruses. Using a combination of replication kinetics, targeted gene expression analyses, and next-generation sequencing, we demonstrate that EFPV establishes a productive infection in both bat and human cells, but that viral replication is more stringently restricted in non-reservoir species. Polyinosinic–polycytidylic acid [poly(I:C)] stimulation prior to infection revealed a robust interferon-dependent antiviral response that limits viral replication in Efk3b and human cells, but not in PaKiT03 cells. Poly(I:C) treatment post-infection showed no significant effect on viral replication in any species. Together, these findings suggest that EFPV is highly adapted to its natural reservoir host, Eptesicus fuscus, but that there exists a zoonotic potential for infection in Pteropus alecto bats and potentially, humans.