Ripley Crake, McMaster University

Ripley Crake, Karen Mossman

Fighting & Responding

Over the past several decades, more than 70% of pathogens infecting humans have been zoonotic in origin. Bats, despite having numerous ecological benefits, are most often recognized for their association with zoonotic disease transmission. Bats have evolved the ability to harbour viruses from at least 28 diverse families while exhibiting limited clinical signs of disease, suggesting that bats may have evolved unique immune characteristics to combat viral infections. One such factor is the positive selection of a serine residue in interferon regulatory factor 3 (IRF3) that enhances antiviral protection. Human cells are exquisitely sensitive in recognizing membrane perturbation during virus particle entry, leading to an innate cellular response that requires IRF3 but is independent of interferon (IFN) and viral replication. Given their enhanced antiviral activity, we hypothesize that bats possess a similar mechanism for viral sensing. Knockout and wild-type Eptesicus fuscus bat cells were treated with UV-inactivated vesicular stomatitis virus (VSV) and herpes simplex virus 1 (HSV1) to test if bat cells induce an antiviral state following membrane perturbation. Antiviral activity was ascertained quantitatively by qPCR of interferon-stimulated genes (ISGs) and qualitatively through visualising fluorescence of a GFP-tagged challenge virus. Preliminary results show that UV-VSV induces significant protection in wild-type bat cells through upregulation of IFNB and antiviral ISGs, while there is no protection in IRF3 KO bat cells. UV-HSV did not provide protection in wild-type or IRF3 KO bat cells.