Project description:Abstract from accompanying publication: "Bats host a number of viruses that cause severe disease in humans without experiencing overt symptoms of disease themselves. While the mechanisms underlying this ability to avoid sickness are not known, deep sequencing studies of bat genomes have uncovered genetic adaptations that may have functional importance in the antiviral response of these animals. Egyptian rousette bats (Rousettus aegyptiacus) are the natural reservoir hosts of Marburg virus (MARV). In contrast to humans, these bats do not become sick when infected with MARV. A striking difference to the human genome is that Egyptian rousettes have an expanded repertoire of IFNW genes. To probe the biological implications of this expansion, we synthesized IFN-ω4 and IFN-ω9 proteins and tested their antiviral activity in Egyptian rousette cells. Both IFN-ω4 and IFN-ω9 showed antiviral activity against RNA viruses, including MARV, with IFN-ω9 being more efficient than IFN-ω4. Using RNA-Seq, we examined the transcriptional response induced by each protein. Although the sets of genes induced by the two IFNs were largely overlapping, IFN-ω9 induced a more rapid and intense response than did IFN-ω4. About 13% of genes induced by IFN-ω treatment are not found in the Interferome or other ISG databases, indicating that they may be uniquely IFN-responsive in this bat."
Project description:Study was performed in order to determine the type and scope of interferon response of Rousettus aegyptiacus-derived fibroblasts to Sendai virus infection. This study helps to understand the function of the expanded immune repertoire of Rosettus aegyptiacus.
Project description:Study was performed in order to determine the scope of antiviral response of Rousettus aegyptiacus-derived fibroblasts to Sendai and Marburg virus infection. This study aids in understanding the function of the expanded immune repertoire of Rosettus aegyptiacus.
Project description:Dermal fibroblasts from bat and human, stimulated with dsRNA (poly(I:C)) and controls. Bats can harbor some of the most deadliest viruses to humans while rarely displaying pathogenicity themselves. To study the transcriptional divergence and cell-to-cell variability of their innate immune response - the expression program that is initiated once a pathogen is sensed, we stimulated dermal fibroblast cells from Rousettus aegyptiacus and from human for four hours with dsRNA - a viral RNA mimic that triggers a rapid innate immune response. Subsequently, we profiled the response using scRNA-seq.
Project description:Bats have adapted to pathogens through diverse mechanisms, including increased resistance - rapid pathogen elimination, and tolerance - limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology) several mechanisms conferring disease tolerance were discovered, but mechanisms underpinning resistance remain poorly understood. Previous studies on other species suggested that elevated basal expression of innate immune genes may lead to increased resistance to infection. Here, we test whether such transcriptional patterns occur in Egyptian fruit bat tissues through single-cell and spatial transcriptomics of gut, lung and blood cells, comparing gene expression between bat, mouse and human. Despite numerous recent loss and expansion events of interferons in the bat genome, interferon expression and induction are remarkably similar to that of mouse. In contrast, central complement system genes are highly and uniquely expressed in key regions in bat lung and gut epithelium, unlike in human and mouse. These genes also evolve rapidly in their coding sequence across the bat lineage. Finally, the bat complement system displays strong hemolytic and inhibitory activities. Together, these results indicate a distinctive transcriptional divergence of the complement system, which may be linked to bat resistance, and highlight the intricate evolutionary landscape of bat immunity.
Project description:This represents the first transcriptomic and epigenomic characterization of the vocalization-associated brain circuits of a non-human mammalian vocal learner (Egyptian fruit bat), yielding fundamental insights into the regulatory and molecular pathways underlying the evolution of complex vocal behavior in mammals.
