Bats are resistant to pathogens, including viruses that cause severe diseases in humans, such as Ebola virus and Coronaviruses. Despite being viral reservoirs, bats rarely fall ill, prompting intense investigations into their immune system. Understanding the mechanisms that allow bats to tolerate viruses will provide a better understanding of the relationships between viruses and their reservoir hosts, and could provide tools to prevent future pandemics.
This project aims at investigating bat innate immune responses, with a focus on Eptesicus genera, which is known to be a reservoir for viruses known to cross species barrier.
To identify innate immune genes expressed in cells from this bat genera, we aim at performing RNA sequencing analysis of cells isolated from Eptesicus serotinus and Eptesicus fuscus, as well as human cells. We hope that this comparative transcriptomics analysis will reveal unique features of chiropteran cells. Some of these identified genes might probably have no known mammalian orthologs while other genes might have orthologs that are not described as immune genes in other mammalian species.
We propose to investigate whether some of these Eptesicus-specific immune genes possess antiviral activities against a panel of viruses, including Eptesicus-borne viruses such as Rio Bravo Virus. We will perform either loss-of-function or gain-of-function approaches to determine whether reduced or increased expression of these genes affect viral replication. We will pick 1 up to 5 candidates that restrict the most efficiently viral replication for further investigations and determine which steps of the viral replication cycle they target using microscopy, biochemistry and virological assays.
Uncovering unique features of bat antiviral program will provide a better understanding of the molecular interplays between bats and viruses, as well as insights into the innate immune responses of important viral reservoirs.
