Misra, VikramBollinger, Trent2023-06-222023-06-2220232023-112023-06-22November 2https://hdl.handle.net/10388/14736There have been numerous pandemics and epidemics throughout human history with varied origins but presently bats are being singled out as the harbingers of current and future plagues. Is there something special about the relationship bats have with their viruses that merits this claim or are they just like other mammals? Bats are unique among mammals in their ability to fly and differences found in their immune system are proposed to be secondary to evolutionary adaptations to flight. These adaptations may allow them to tolerate viruses without developing associated disease. The large numbers of viruses found across bat species could reflect this tolerance, but it may also reflect the sheer number of bat species and therefore viruses of this mammalian order. The perceived tolerance could also reflect our limited understanding of infectious diseases in bats. To address this question, we reviewed the literature on viral diseases in bats, looked for pathological changes that were potentially associated with viral infection in routine post-mortem evaluations of Western Canadian bats, and examined the innate response to DNA in big brown bat cells. We isolated two DNA viruses from naturally infected big brown bats. One, a herpesvirus, was not associated with any disease and the other, a poxvirus, was associated with oral ulcerations and joint swelling. Novel features were noted with both viruses: an atypical cell type supporting replication for the herpesvirus and an abnormal cellular site of replication for the poxvirus. Big brown bat cells expressed an array of DNA sensors and used multiple transcription factors to generate an innate response to a DNA surrogate. These bat cells produced a comparable innate response when they were infected with inactivated forms of these viruses. Whereas the innate of response of human cells stimulated with this surrogate was markedly proinflammatory. This proinflammatory induction was not observed in bat cells. One of these proinflammatory products, interleukin 8, was expressed at high levels in bat cells independent of treatment, including viral infections. A different proinflammatory product, interleukin 6, was inhibited in response to the DNA surrogate, but the inhibition was overcome upon infection with live poxvirus. The herpesvirus, which was not associated with any pathological changes, was able to control the innate response, whereas the poxvirus, which was associated with disease, was not. This work suggests bats are susceptible to disease caused by viruses, they are not generally tolerant to viruses, and the development of disease is dependent on the type of virus, which is similar to other mammalian species.application/pdfenChiropterabig brown batEptesicus fuscus gammaherpesvirusEptesipox virusinnate immune responsein-situ hybridizationpulmonary intravascular macrophageultrastructurevirusThesis2023-06-22