Comparison of antiviral responses in two bat species reveals conserved and divergent innate immune pathways

Schneor, Lilach; Kaltenbach, Stefan; Friedman, Sivan; Tussia-Cohen, Dafna; Nissan, Yomiran; Shuler, Gal; Fraimovitch, Evgeny; Kolodziejczyk, Aleksandra A.; Weinberg, Maya; Donati, Giacomo; Teeling, Emma C.; Yovel, Yossi; Hagai, Tzachi

doi:10.1016/j.isci.2023.107435

Cited by 6 publications

(2 citation statements)

References 108 publications

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“…We next searched for innate immune genes that differ in expression between R. aegyptiacus, human and mouse. Steady-state expression of immune genes in barrier tissues can have important consequences for species ability to resist invading pathogens, and is thought to be an important mechanism in the adaptation of several bat species to viral infection 64,65 . We found that in contrast to the to the majority of innate immune genes that do not significantly differ in steady-state expression between the species in either lung or gut cells, many complement system genes are uniquely expressed in bat epithelial cells from both tissues.…”

Section: Discussionmentioning

confidence: 99%

Spatial and single-cell transcriptomics illuminate bat immunity and barrier tissue evolution

Levinger,

Tussia-Cohen,

Friedman

et al. 2023

Preprint

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The Egyptian fruit bat displays tolerance to lethal viruses and unique dietary adaptations, but the molecular basis for this is poorly understood. To this end, we generated detailed maps of bat gut, lung and blood cells using spatial and single-cell transcriptomics. We compared bat with mouse and human cells to reveal divergence in genetic programs associated with environmental interactions and immune responses. Complement system genes are transcriptionally divergent, uniquely expressed in bat lung and gut epithelium, and undergo rapid coding-sequence evolution. Specifically in the tip of the gut villus, bat enterocytes express evolutionarily young genes while lacking expression of genes related to specific nutrient absorption. Profiling immune stimulation of PBMCs revealed a monocyte subset with conserved cross-species interferon expression, suggesting strong constraints to avoid an excessive immune response. Our study thus uncovers conserved and divergent immune pathways in bat tissues, providing a unique resource to study bat immunity and evolution.

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Section: Discussionmentioning

confidence: 99%

Spatial and single-cell transcriptomics illuminate bat immunity and barrier tissue evolution

Levinger,

Tussia-Cohen,

Friedman

et al. 2023

Preprint

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“…These viruses can undergo cross-species transmission and pose pathogenicity risks to other mammals, including human, through direct contact or intermediate hosts (Cui et al, 2019;Tian et al, 2022). Comparative genomic studies have explored genomic evidence of virus tolerance in the ancestral Chiroptera (Zhang et al, 2013;Jebb et al 2020;Scheben et al 2020;Moreno Santillan et al, 2021), revealing unique immune system adaptations in bats, such as the loss of the PHYIN gene family (Zhang et al, 2013;Ahn et al, 2016), expansions and contractions of type I IFN cytokines (Zhou et al, 2016;Pavlovich et al, 2018), as well as expansion of Tetherin (Hayward et al, 2022), PKR (Jacquet et al, 2022) and TNFRSF14 (Schneor et al, 2023). Given that the majority of identified viruses (~80%) are hosted by Vespertilionidae, Rhinolophidae and Pteropodidae families, focusing on bats from these specific clades may provide novel insights into the evolution and adaptive divergence of virus tolerance (Tian et al, 2022, Tian et al, 2023.…”

Section: Discussuionmentioning

confidence: 99%

Chromosome-level genome and population genomics of the intermediate horseshoe bat (<i>Rhinolophus affinis)</i> reveal the molecular basis of virus tolerance in <i>Rhinolophus</i> and echolocation call frequency variation

Zhao,

Yuan,

Wang

et al. 2024

Zoological Research

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Horseshoe bats (genus Rhinolophus, family Rhinolophidae) represent an important group within the bat families. These bats have several notable characteristics that distinguish them from other bats, such as the specialized high constant frequency echolocation calls, rapid karyotype evolution, as well as the increasing reports about the their unique immune system.Evolutionary studies supported by high-quality reference genome and whole-genome data provide deeper insights into species origin, speciation, adaptive evolution, and phenotypic variation. However, so far, the genomic data limitation of only one published genome of the horseshoe bat, R. ferrumequinum, creates obstacles for a deeper understanding of the evolutionary patterns in Rhinolophus. In this research, we constructed a high-quality chromosome-level reference genome for the intermediate horseshoe bat (R. affinis). Our comparative genomic analyses revealed potential genetic characteristics associated with virus tolerance in Rhinolophidae. This includes the expansion of several gene families related to immune response, as well as the identification of genes functionally associated with the SARS-CoV-2 signaling pathway, DNA repair, and apoptosis that exhibit signs of rapid evolution. In addition, we observed an expansion of the MHC-2 region and a higher copy number of the HLA-DQB2 gene in horseshoe bats compared to other bats. By generating whole-genomic resequencing data for population genomic analyses, we identified multiple candidate loci (e.g. GLI3) associated with echolocation call frequency variation across R. affinis subspecies. Our work has expanded the understanding of the genetic characteristics of the horseshoe bat group, while also provides a data foundation for future research.

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Establishing Primary and Stable Cell Lines from Frozen Wing Biopsies for Cellular, Physiological, and Genetic Studies in Bats

Deng,

Morales‐Sosa,

Bernal‐Rivera

et al. 2024

Current Protocols

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Bats stand out among mammalian species for their exceptional traits, including the capacity to navigate through flight and echolocation, conserve energy through torpor/hibernation, harbor a multitude of viruses, exhibit resistance to disease, survive harsh environmental conditions, and demonstrate exceptional longevity compared to other mammals of similar size. In vivo studies of bats are challenging for several reasons, such as difficulty in locating and capturing them in their natural environments, limited accessibility, low sample size, environmental variation, long lifespans, slow reproductive rates, zoonotic disease risks, species protection, and ethical concerns. Thus, establishing alternative laboratory models is crucial for investigating the diverse physiological adaptations observed in bats. Obtaining quality cells from tissues is a critical first step for successful primary cell derivation. However, it is often impractical to collect fresh tissue and process the samples immediately for cell culture due to the resources required for isolating and expanding cells. As a result, frozen tissue is typically the starting resource for bat primary cell derivation, but cells in frozen tissue are usually damaged and have low integrity and viability. Isolating primary cells from frozen tissues thus poses a significant challenge. Herein, we present a successfully developed protocol for isolating primary dermal fibroblasts from frozen bat wing biopsies. This protocol marks a significant milestone, as this is the first protocol specifically focused on fibroblast isolation from bat frozen tissue. We also describe methods for primary cell characterization, genetic manipulation of primary cells through lentivirus transduction, and the development of stable cell lines. © 2024 Wiley Periodicals LLC.Basic Protocol 1: Bat wing biopsy collection and preservationSupport Protocol 1: Blood collection from bat venipunctureBasic Protocol 2: Isolation of primary fibroblasts from adult bat frozen wing biopsySupport Protocol 2: Primary fibroblast culture and subcultureSupport Protocol 3: Determination of growth curve and doubling timeSupport Protocol 4: Cell banking and thawing of primary fibroblastsBasic Protocol 3: Lentiviral transduction of bat primary fibroblastsBasic Protocol 4: Bat stable fibroblast cell line developmentSupport Protocol 5: Bat fibroblast validation by immunofluorescence stainingBasic Protocol 5: Chromosome counting

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Comparison of antiviral responses in two bat species reveals conserved and divergent innate immune pathways

Cited by 6 publications

References 108 publications

Spatial and single-cell transcriptomics illuminate bat immunity and barrier tissue evolution

Spatial and single-cell transcriptomics illuminate bat immunity and barrier tissue evolution

Chromosome-level genome and population genomics of the intermediate horseshoe bat (<i>Rhinolophus affinis)</i> reveal the molecular basis of virus tolerance in <i>Rhinolophus</i> and echolocation call frequency variation

Establishing Primary and Stable Cell Lines from Frozen Wing Biopsies for Cellular, Physiological, and Genetic Studies in Bats

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