Host–virus determinants of Ebola virus persistence in a human cerebral organoid model
Year: 2026
Type: article
Abstract: Ebola virus (EBOV) causes Ebola virus disease (EVD), a multisystemic human disease associated with an extraordinarily high case-fatality rate. EVD survivors may experience recrudescent inflammation with viral persistence in immune-privileged tissues, including the central nervous system (CNS). Persistence, defined by ongoing replication of the EBOV genome beyond the acute disease phase, may lead to virion production. Productive persistence has been linked to re-initiation of EVD outbreaks. We developed a human cerebral organoid model to investigate the host and viral determinants of EBOV CNS persistence. In this model, EBOV persistence for 120 days was sustained by continuous infection of astrocytes and neurons and the recruitment and infection of microglia. This was accompanied by the emergence of EBOV defective viral genomes and genomic subvariants, cell-to-cell transmission, activation of cell-specific innate immunity, and late brain organoid inflammation, indicating that persistent infection of EBOV within immune-privileged niches drives local inflammation.
Source: Nature Microbiology
Authors: Lina Widerspick, Santiago Vidal Freire, Johanna F. Steffen, Shruti Shirsathe, Petra Allartz, Molly A. Vickers, Christoph Henkel, Pedro Neira Pelén, Julia Nave, Monika Rottstegge, Michelle Heung, Stephanie Wurr, Dennis Tappe, Lisa Oestereich, Jonas Müller, Angelique Hoelzemer, Leonore Mensching, Thomas Hoenen, Nicole C. Kleinstreuer, Ian Crozier, John G. Bernbaum, Gabriella Worwa, Jens H. Kuhn, Gustavo Palacios, César Muñoz-Fontela
Institutions: German Center for Infection Research, Institut für Mikrobiologie der Bundeswehr, Bernhard Nocht Institute for Tropical Medicine, Icahn School of Medicine at Mount Sinai, University Medical Center Hamburg-Eppendorf, Leibniz Institute of Virology (LIV), Friedrich-Loeffler-Institut, National Institutes of Health, Division of Program Coordination Planning and Strategic Initiatives, Frederick National Laboratory for Cancer Research, National Institute of Allergy and Infectious Diseases
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7164575454