A Synthetic Consensus Chiroptera IFN-β Induces IFN-I Signaling Across Diverse Bat Taxa

Bat-associated viruses consistently spill over from bats into humans and other animals. Many bat-associated viruses, including Marburg virus and Nipah virus, cause severe disease in humans but their presentation is subclinical in bats. Advancements in tools and resources to study bat innate antiviral immune responses, including the type I IFN (IFN-I) pathway, are needed to evaluate the mechanisms that underlie differential infection outcomes between reservoir bats and spillover hosts. Commercially available IFN-Is are not bat-specific, and conspecific IFN-Is are impractical to produce for the over 1,500 described bat species. Here, we design and validate a bat order-level consensus IFN (Chiroptera IFN-β) that is functional in bat cells from six diverse bat families, including representatives from both suborders. Using Jamaican fruit bat cells, we demonstrate that Chiroptera IFN-β induces an IFN-stimulated gene repertoire comparable to conspecific IFN-β. This valuable resource can accelerate the capacity of the field to study bat innate antiviral responses and illuminate differences between bats and humans.