Journal Article

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

Loyer, Clara, Krchlikova, Veronika, Vazquez, Juan Manuel, Rey, Carine, Gray-Sandoval, Genavieve, Le Corf, Amandine, Maesen, Sarah, Enard, David, Etienne, Lucie, Sareoua, Lucas, Sudmant, Peter H., Lauterbur, M. Elise, Cimarelli, Andrea, Chantharath, Amandine

2026

Overview

Bats are asymptomatic reservoirs of several zoonotic viruses. This may result from long-term co-evolution between viruses and bats, that have led to host adaptations contributing to an effective balance between strong antiviral responses with innate immune tolerance. To better understand these virus-host interactions, we combined comparative transcriptomics, phylogenomics and functional assays to characterize the evolution of bat innate immune antiviral factors. First, we stimulated the type I interferon immune pathway in Myotis yumanensis primary cells and identified guanylate-binding protein 5 (GBP5) as the most differentially expressed interferon-stimulated gene (ISG). Phylogenomic analyses showed that bat GBP5 has been under strong episodic positive selection, with numerous rapidly evolving sites and species-specific gene duplications, suggesting past evolutionary arms races. Functional tests on GBP5 orthologs from 10 bat species covering the >60 million years of Chiroptera evolution revealed species- and virus-specific restrictions against RNA viruses (retrovirus HIV, and rhabdoviruses European bat lyssavirus and VSV), which are typical signatures of adaptations to past viral epidemics. Interestingly, we also observed a lineage-specific loss of the GBP5 prenylation motif in the common ancestor of Pipistrellus and Eptesicus bats. Importantly, resurrection of the prenylation motif in Eptesicus fuscus GBP5 in corresponding bat cells was associated with different GBP5 subcellular localization and loss of anti-rhabdoviral functions, suggesting specific adaptation to ancient viral epidemics ~22 million years ago. Altogether, our results highlight adaptations that contribute to bat specific immunity and provide insights into the functional evolution of antiviral effector GBP5.

• Publisher: Public Library of Science,PLOS,Public Library of Science (PLoS)
• Subject: Animals / Bats / Binding proteins / Biological response modifiers / Biology and Life Sciences / Chiroptera - genetics / Chiroptera - immunology / Chiroptera - virology / Evolution, Molecular / Genes / Genomics / GTP-Binding Proteins - genetics / GTP-Binding Proteins - immunology / GTP-Binding Proteins - metabolism / Health aspects / HIV (Viruses) / Host-virus relationships / Immune system / Immunity, Innate - genetics / Immunotherapy / Interferon / Medicine and Health Sciences / Phylogeny / Physical Sciences / Physiological aspects / Protein binding / Research and Analysis Methods / RNA / RNA viruses