Lasso Gorka, Grodus Michael, Valencia Estefania, DeJesus Veronica, Liang Eliza, Delwel Isabel, Bortz Rob H, Lupyan Dmitry, Ehrlich Hanna Y, Castellanos Adrian A, Gazzo Andrea, Wells Heather L, Wacharapluesadee Supaporn, Tremeau-Bravard Alexandre, Seetahal Janine F R, Hughes Tom, Lee Jimmy, Lee Mei-Ho, Sjodin Anna R, Geldenhuys Marike, Mortlock Marinda, Navarrete-Macias Isamara, Gilardi Kirsten, Willig Michael R, Nava Alessandra F D, Loh Elisabeth H, Asrat Makda, Smiley-Evans Tierra, Magesa Walter S, Zikankuba Sijali, Wolking David, Suzán Gerardo, Ojeda-Flores Rafael, Carrington Christine V F, Islam Ariful, Epstein Jonathan H, Markotter Wanda, Johnson Christine K, Goldstein Tracey, Han Barbara A, Mazet Jonna A K, Jangra Rohit K, Chandran Kartik, Anthony Simon J
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
Cell Host Microbe. 2025 Feb 12;33(2):294-313.e11. doi: 10.1016/j.chom.2024.12.016. Epub 2025 Jan 15.
Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species. We found that GP-NPC1 binding correlated poorly with phylogeny. By integrating binding assays with machine learning, we identified genetic factors influencing virus-receptor-binding and predicted GP-NPC1-binding avidity for additional filoviruses and bats. Moreover, combining receptor-binding avidities with bat geographic distribution and the locations of previous Ebola outbreaks allowed us to rank bats by their potential as Ebola virus hosts. This study represents a comprehensive investigation of filovirus-receptor binding in bats (1,484 GP-NPC1 pairs, 11 filoviruses, and 135 bats) and describes a multidisciplinary approach to predict susceptible species and guide filovirus host surveillance.
有证据表明蝙蝠是丝状病毒的重要宿主，但具体涉及的物种在很大程度上仍未明确。尼曼-匹克病C1型（NPC1）是一种关键的进入受体，其氨基酸变异会影响病毒易感性和物种特异性嗜性。在此，我们对来自81种蝙蝠的七种丝状病毒糖蛋白（GPs）和NPC1直系同源物进行了组合结合研究。我们发现GP-NPC1结合与系统发育的相关性较差。通过将结合试验与机器学习相结合，我们确定了影响病毒-受体结合的遗传因素，并预测了其他丝状病毒和蝙蝠的GP-NPC1结合亲和力。此外，将受体结合亲和力与蝙蝠地理分布以及以往埃博拉疫情爆发地点相结合，使我们能够根据蝙蝠作为埃博拉病毒宿主的潜力对其进行排名。这项研究代表了对蝙蝠中丝状病毒-受体结合的全面调查（1484对GP-NPC1、11种丝状病毒和135种蝙蝠），并描述了一种多学科方法来预测易感物种并指导丝状病毒宿主监测。
