Bat goblet cells as immuno-hotspots for infection of coronavirus
Professor of Conservation Biology
I’m interested in how biology and the environment shape biodiversity in time and space.
- Global Union of Bat Diversity Networks (GBatNet)
- Integrated mechanisms of environment-host-virome interactions
- Immunological adaptations in bats to moderate the effect of coronavirus infection
- Regrowing the brain; evolution and mechanisms of seasonal reversible size changes in a mammal
- Genomics of exceptions to scaling of longevity to body size
High viral tolerance coupled with an extraordinary regulation of the immune response makes bats a great model to study host-pathogen evolution. Although many immune-related gene gains and losses have been previously reported in bats, important gene families such as antimicrobial peptides (AMPs) remain understudied. We built an exhaustive bioinformatic pipeline targeting the major gene families of defensins and cathelicidins to explore AMP diversity and analyze their evolution and distribution across six bat families. A combination of manual and automated procedures identified 29 AMP families across queried species, with α-, β-defensins, and cathelicidins representing around 10% of AMP diversity. Gene duplications were inferred in both α-defensins, which were absent in five species, and three β-defensin gene subfamilies, but cathelicidins did not show significant shifts in gene family size and were absent in Anoura caudifer and the pteropodids. Based on lineage-specific gains and losses, we propose diet and diet-related microbiome evolution may determine the evolution of α- and β-defensins gene families and subfamilies. These results highlight the importance of building species-specific libraries for genome annotation in non-model organisms and shed light on possible drivers responsible for the rapid evolution of AMPs. By focusing on these understudied defenses, we provide a robust framework for explaining bat responses to pathogens.
Bats carry viruses that can cause severe disease in other mammals. Asymptomatic infections in bats suggest limited tissue-damaging inflammation and immunopathology. To investigate the genomic basis of disease resistance, the Bat1K project generated reference-quality genomes of ten bat species. A systematic analysis showed that signatures of selection in immune genes are more prevalent in bats compared with other mammals. We found an excess of immune gene adaptations in the ancestral Chiroptera and many descending bat lineages, highlighting viral entry and detection factors, and regulators of antiviral and inflammatory responses. ISG15, an antiviral gene contributing to hyperinflammation during COVID-19, exhibits a deletion of a cysteine, required for homodimer formation, in rhinolophid and hipposiderid bats. Cellular infection experiments showed enhanced intracellular protein conjugation of bat ISG15 and lack of secretion into extracellular space, where human ISG15 stimulates inflammation. Our work highlights molecular mechanisms contributing to viral tolerance and disease resistance in bats.
Ariadna E. Morales, Yue Dong, Thomas Brown, Kaushal Baid, Dimitrios - Georgios Kontopoulos, Victoria Gonzalez, Zixia Huang, Alexis-Walid Ahmed, Leon Hilgers, Sylke Winkler, Graham M. Hughes, Xiaomeng Li, Bogdan M. Kirilenko, Paolo Devanna, Tanya M. Lama, Yomiran Nissan, Martin Pippel, Liliana M. Dávalos, Sonja C. Vernes, Sebastien J. Puechmaille, Stephen J. Rossiter, Yossi Yovel, Joseph B. Prescott, Andreas Kurth, David A. Ray, Burton K. Lim, Eugene Myers, Emma C. Teeling, Arinjay Banerjee, Aaron T. Irving, Michael Hiller
Diversity in olfactory receptor repertoires is associated with dietary specialization in a genus of frugivorous bat
Mammalian olfactory receptors (ORs) are a diverse family of genes encoding proteins that directly interact with environmental chemical cues. ORs evolve via gene duplication in a birth-death fashion, neofunctionalizing and pseudogenizing over time. Olfaction is a primary sense used for food detection in plant-visiting bats, but the relationship between dietary specialization and OR repertoire diversity is unclear. Within neotropical Leaf-nosed bats (Phyllostomidae), many lineages are plant specialists, and some have a distinct OR repertoire compared to insectivorous species. Yet, whether specialization on particular plant genera is associated with the evolution of specialized OR repertoires with narrower diversity has never been tested. Using targeted sequence capture, we sequenced the OR repertoires of three sympatric species of short-tailed fruit bats (Carollia), which vary in their degree of specialization on the fruits of Piper plants. We characterized orthologous versus duplicated receptors among Carollia species, and explored the diversity and redundancy of the receptor gene repertoire. At the species level, the most dedicated Piper specialist, Carollia castanea, had lower OR diversity compared to the two generalists (C. sowelli, C. perspicillata), but we discovered a few unique sets of ORs within C. castanea with high redundancy of similar gene duplicates. These unique receptors potentially enable C. castanea to detect Piper fruit odorants better than its two congeners. Carollia perspicillata, the species with the most generalist diet, had a higher diversity of intact receptors, suggesting the ability to detect a wider range of odorant molecules. Variation among ORs may be a factor in the coexistence of these sympatric species, facilitating the exploitation of different plant resources. Our study sheds light on how gene duplication and changes in OR diversity may play a role in dietary adaptations and underlies patterns of ecological interactions between bats and plants.
Comprising more than 1,400 species, bats possess adaptations unique among mammals including powered flight, unexpected longevity, and …
Diana D. Moreno-Santillán, Tanya Lama, Yocelyn Gutiérrez Guerrero, Alexis Brown, Paul Donat, Huabin Zhao, Stephen Rossiter, Laurel R. Yohe, Joshua Potter, Emma C. Teeling, Sonja Vernes, Kalina T.J. Davies, Eugene Myers, Graham M. Hughes, Zixia Huang, Federico G. Hoffmann, Angelique P. Corthals, David Ray, Liliana M. Dávalos