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:Bats are natural hosts for a wide diversity of viruses. While many of these viruses are highly pathogenic in humans, most do not appear to cause major symptoms in bats. These modern bat-specific characteristics are the result of past virus-host (co)evolution and virus-driven host adaptations. Innate immunity is the first line of defense against viruses in mammals, we aim at characterizing bat innate immunity in response to viruses. Using genome-wide and gene candidate evolutionary analyses, we found that many bat antiviral genes have undergone multiple duplication events in a lineage-specific manner, specifically in the Myotis bat lineage. We focus on Myotis yumanensis as a model in the Myotis lineage. We performed transcriptomic analyses and observed the upregulation of most mammalian genes implicated in the different steps of the innate immune response from sensing to interferon-stimulated genes (ISGs), showing the conservation of the core innate immunity. Our study will contribute to identifying adaptations that shaped bat innate immunity. These adaptations may contribute to the bat-virus specificity and influence viral emergence to another mammalian host
Project description:Bats are tolerant to highly pathogenic viruses such as Marburg, Ebola, and Nipah, suggesting the presence of a unique immune tolerance toward viral infection. Here, we compared SARS-CoV-2 infection of human and bat (Rhinolophus ferrumequinum) pluripotent cells and fibroblasts. Since bat cells do not express an ACE2 receptor that allows virus infection, we transduced the human ACE2 receptor into the cells and found that transduced cells can be infected with SARS-CoV-2. Compared to human ESCs-hA, infected bat iPSCs-hA produced about a 100-fold lower level of infectious virus and displayed lower toxicity. In contrast, bat fibroblasts (BEF-hA) produced no infectious virus while being infectable and synthesizing viral RNA and proteins, suggesting abortive infection. Indeed, electron microscopy failed to detect virus-like particles in infected bat fibroblasts in contrast to bat iPSCs or human cells, consistent with the latter producing infectious viruses. This suggests that bat somatic but not pluripotent cells have an effective mechanism to control virus replication. Consistent with previous results by others, we find that bat cells have a constitutively activated innate immune system, which might limit SARS-CoV-2 infection compared to human cells.