Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning.

Journal: Cell host & microbe
PMID: 39818205

Abstract

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.

Authors

  • Gorka Lasso
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA. Electronic address: gorka.lasso@gmail.com.
  • Michael Grodus
    Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
  • Estefania Valencia
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
  • Veronica DeJesus
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
  • Eliza Liang
    Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
  • Isabel Delwel
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
  • Rob H Bortz
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
  • Dmitry Lupyan
    Schrödinger Inc., Cambridge, MA 02142, USA.
  • Hanna Y Ehrlich
    One Health Institute, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Adrian A Castellanos
    Cary Institute of Ecosystem Studies, Millbrook, NY 12545, USA.
  • Andrea Gazzo
    Interuniversity Institute for Bioinformatics in Brussels, ULB-VUB, 1050 Brussels, Belgium; Machine Learning Group, Université Libre de Bruxelles, 1050 Brussels, Belgium; Center for Medical Genetics, Reproduction and Genetics, Reproduction Genetics and Regenerative Medicine, Vrije Universiteit Brussel, UZ Brussel, 1050 Brussels, Belgium.
  • Heather L Wells
    Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Supaporn Wacharapluesadee
    Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
  • Alexandre Tremeau-Bravard
    One Health Institute, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Janine F R Seetahal
    Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502, USA.
  • Tom Hughes
    Conservation Medicine, 47000 Sungai Buloh, Selangor, Malaysia; EcoHealth Alliance, New York, NY 10018, USA.
  • Jimmy Lee
    Institute of Mental Health, Singapore, Singapore.
  • Mei-Ho Lee
    Conservation Medicine, 47000 Sungai Buloh, Selangor, Malaysia; EcoHealth Alliance, New York, NY 10018, USA.
  • Anna R Sjodin
    Department of Ecology and Evolutionary Biology, University of Connecticut, Storrs, CT 06269, USA.
  • Marike Geldenhuys
    Centre for Viral Zoonoses, Department of Medical Virology, University of Pretoria, Pretoria 0001, South Africa.
  • Marinda Mortlock
    Centre for Viral Zoonoses, Department of Medical Virology, University of Pretoria, Pretoria 0001, South Africa.
  • Isamara Navarrete-Macias
    Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Kirsten Gilardi
    One Health Institute, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Michael R Willig
    Department of Ecology and Evolutionary Biology, University of Connecticut, Storrs, CT 06269, USA; Center for Environmental Sciences and Engineering, Institute of the Environment, University of Connecticut, Storrs, CT 06269, USA.
  • Alessandra F D Nava
    Fundação Oswaldo Cruz-Fiocruz, Instituto Leônidas & Maria Deane, Laboratório de Ecologia de Doenças Transmissíveis na Amazônia - EDTA, Manaus 69.057-070, AM, Brazil.
  • Elisabeth H Loh
    Division of Natural Sciences and Mathematics, Transylvania University, Lexington, KY 40508, USA.
  • Makda Asrat
    Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Tierra Smiley-Evans
    One Health Institute, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Walter S Magesa
    College of Veterinary Medicine and Biomedical Sciences, Sokoine University of Agriculture, P.O. Box 3021, Morogoro, Tanzania.
  • Sijali Zikankuba
    College of Veterinary Medicine and Biomedical Sciences, Sokoine University of Agriculture, P.O. Box 3021, Morogoro, Tanzania.
  • David Wolking
    One Health Institute, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Gerardo Suzán
    Laboratorio de Ecología de Enfermedades y Una Salud, Departamento de Etología, Fauna Silvestre y Animales de Laboratorio, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico.
  • Rafael Ojeda-Flores
    Laboratorio de Ecología de Enfermedades y Una Salud, Departamento de Etología, Fauna Silvestre y Animales de Laboratorio, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico.
  • Christine V F Carrington
    Department of Preclinical Sciences, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Republic of Trinidad and Tobago.
  • Ariful Islam
    Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
  • Jonathan H Epstein
    EcoHealth Alliance, New York, NY 10018, USA.
  • Wanda Markotter
    Centre for Viral Zoonoses, Department of Medical Virology, University of Pretoria, Pretoria 0001, South Africa.
  • Christine K Johnson
    One Health Institute, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Tracey Goldstein
    One Health Institute, Colorado State University, Fort Collins, CO 80523, USA.
  • Barbara A Han
    Cary Institute of Ecosystem Studies, Millbrook, NY 12545.
  • Jonna A K Mazet
    One Health Institute, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
  • Rohit K Jangra
    Department of Microbiology and Immunology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71103, USA; Center for Applied Immunology and Pathological Processes, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71103, USA; Center of Excellence for Emerging Viral Threats, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71103, USA. Electronic address: rohit.jangra@lsuhs.edu.
  • Kartik Chandran
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA. Electronic address: kartik.chandran@einsteinmed.edu.
  • Simon J Anthony
    Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. Electronic address: sjanthony@ucdavis.edu.

Keywords

External Resources

Popular Topics
Recent Journals