Genomic and functional adaptations in guanylate-binding protein 5 (GBP5) highlight specificities of bat antiviral innate immunity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Bats are asymptomatic reservoirs of several zoonotic viruses. This may result from long-term coevolution between viruses and bats, that have led to host adaptations contributing an effective balance strong antiviral responses with innate immune tolerance. To better understand these virus-host interactions, we combined comparative transcriptomics, phylogenomics functional assays characterize the evolution bat factors. First, stimulated type I interferon pathway in Myotis yumanensis primary cells identified guanylate-binding protein 5 (GBP5) as most differentially expressed interferon-stimulated gene (ISG). Phylogenomic analyses showed GBP5 has been under episodic positive selection, numerous rapidly evolving sites species-specific duplications, suggesting past evolutionary arms races. Functional tests on orthologs ten species covering >60 million years Chiroptera revealed species- virus-specific restrictions against RNA (retrovirus HIV, rhabdoviruses European lyssavirus VSV), which typical signatures viral epidemics. Interestingly, also observed a lineage-specific loss prenylation motif common ancestor Pipistrellus Eptesicus associated different subcellular localization functions. Resurrection ancestral fuscus rescued its localization, but not complete activities, additional determinants necessary for restriction. Altogether, our results highlight contribute specific immunity provide insights into effector GBP5. is upon stimulation cells. Bat evolved genomic genetic diversification, including early stop codon leading truncation motif.GBP5 diversification bats impacts their functions.Bat GBP5s exhibit virus-specificity ability inhibit infectivity particles, bearing glycoproteins retroviral vesicular stomatitis virus lyssavirus-1.Resurrection rescues full activity.

Language: Английский

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Expanding the bat toolbox: Carollia perspicillata bat cell lines and reagents enable the characterization of viral susceptibility and innate immune responses

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(4), P. e3003098 - e3003098

Published: April 15, 2025

Multiple viruses that are highly pathogenic in humans known to have evolved bats. How bats tolerate infection with these viruses, however, is poorly understood. As engage a wide range of interactions their hosts, it essential study bat system resembles natural environment like bat-derived vitro cellular models. However, stable and accessible cell lines not widely available for the broader scientific community. Here, we generated reagents Seba’s short-tailed ( Carollia perspicillata ), tested multiple methods immortalization, characterized susceptibility virus response immune stimulation. Using pseudotyped library authentic infections, show C. derived from diverse array tissues susceptible bearing glycoprotein numerous orthohantaviruses, including Andes Hantaan also live hantavirus infection. Furthermore, stimulation synthetic double-stranded RNA prior vesicular stomatitis Middle Eastern respiratory syndrome coronavirus induced protective antiviral response, demonstrating suitability our response. Taken together, approaches outlined here will inform future efforts develop tools virology non-model organisms enable studies on virus–host

Language: Английский

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<i>Myotis</i> bat STING attenuates aging-related inflammation in female mice

动物学研究, Journal Year: 2024, Volume and Issue: 45(5), P. 961 - 971

Published: Jan. 1, 2024

Bats, notable as the only flying mammals, serve natural reservoir hosts for various highly pathogenic viruses in humans (e.g., SARS-CoV and Ebola virus). Furthermore, bats exhibit an unparalleled longevity among mammals relative to their size, particularly

Language: Английский

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Bats as instructive animal models for studying longevity and aging

Annals of the New York Academy of Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Abstract Bats (order Chiroptera) are emerging as instructive animal models for aging studies. Unlike some common laboratory species, they meet a central criterion studies: live long time in the wild or captivity, 20, 30, and even >40 years. Healthy (i.e., healthspan) bats has drawn attention to their potential improve lives of humans due bat imperviousness viral infections, apparent low rate tumorigenesis, unique ability repair DNA. At same time, longevity also permits accumulation age‐associated systemic pathologies that can be examined detail manipulated, especially captive animals. Research uncovered additional critical advantages bats. In multiple ways, better analogs than rodents. this review, we highlight eight diverse areas research with relevance aging: genome sequencing, telomeres, DNA repair; immunity inflammation; hearing; menstruation menopause; skeletal system fragility; neurobiology neurodegeneration; stem cells; senescence mortality. These examples demonstrate broad an model point directions particularly important human

Language: Английский

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Studying bats using a One Health lens: bridging the gap between bat virology and disease ecology

Journal of Virology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

ABSTRACT Accumulating data suggest that some bat species host emerging viruses are highly pathogenic in humans and agricultural animals. Laboratory-based studies have highlighted important adaptations immune systems allow them to better tolerate viral infections compared humans. Simultaneously, ecological discovered critical extrinsic factors, such as nutritional stress, correlate with virus shedding wild-caught bats. Despite progress independently understanding the role of bats reservoirs viruses, there remains a significant gap molecular factors drive spillover from Driven by collective goal bridging between fields virology, immunology, disease ecology, we hosted satellite symposium at 2024 American Society for Virology meeting. Bringing together virologists, immunologists, ecologists, discussed intrinsic receptor engagement, adaptive immunity, ecology influence hosts. This article summarizes topics during emphasizes need interdisciplinary collaborations resource sharing.

Language: Английский

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