Cell intrinsic antiviral immunity in diverse bats

Project Summary Bats serve as reservoirs for numerous viruses that spill over to humans and cause disease. The immune adaptations that allow bats to control viral infections without developing disease are not clearly defined. This project aims to investigate cell-intrinsic antiviral mechanisms in bats, focusing on interferon-stimulated genes (ISGs) and their evolutionary adaptations. We will examine the antiviral properties of RTP4, a rapidly evolving RNA-binding protein that inhibits flaviviruses, which have been associated with bats for decades but are relatively understudied compared to other viral zoonoses. Through biochemical, genetic, virological, and cell biological approaches, we will determine the antiviral molecular mechanism of RTP4 and assess the functional diversity of ISGs across multiple bat species. Successful completion of this project will significantly advance our understanding of bat immunity by defining the molecular mechanisms underlying a bat-flavivirus arms race, and by expanding the known repertoire of antiviral bat ISGs. These outcomes will set the stage for future mechanistic studies and may inform strategies to combat zoonotic disease.