Project description:Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigated the antiviral RNA interference (RNAi) pathway in bat cells and discovered that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs (vsiRNAs) upon Sindbis virus (SINV) infection that were missing in human cells. Disruption of Dicer function resulted in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors (PRRs), such as retinoic acid-inducible gene I (RIG-I), with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.
Project description:SARS-CoV-2 emerged in humans in late 2019 and was rapidly followed by spillback into naive wildlife, leading to both mortality events and novel enzootic cycles. Of special concern is whether SARS-CoV-2 could establish in bats in the Americas, given that sarbecoviruses coevolved with rhinolophid bats in the Eastern Hemisphere. We analyzed residual plasma samples from a previous SARS-CoV-2 challenge study of Mexican free-tailed bats (Tadarida brasiliensis) to identify candidate protein biomarkers of susceptibility and assessed the abundance of these same proteins in a wild population of this bat species in Texas. Using 2 uL plasma volumes, we generated proteomes from captive (n = 20; four resistant, five susceptible, 11 unchallenged) and wild (n = 15) bats using the S-Trap method and LC-MS/MS, identifying 475 proteins using data-independent acquisition and a species-specific genome annotation generated by the Bat1K Project.
Project description:Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigated the antiviral RNA interference (RNAi) pathway in bat cells and discovered that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs (vsiRNAs) upon Sindbis virus (SINV) infection that were missing in human cells. Disruption of Dicer function resulted in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors (PRRs), such as retinoic acid-inducible gene I (RIG-I), with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.