Broad-spectrum antiviral brincidofovir inhibits Epstein-Barr virus and related gammaherpesvirus in human and nonhuman primate cells
Epstein-Barr virus (EBV) is of growing interest for its potential role in neurodegenerative diseases such as multiple sclerosis (MS) and its possible utility as a therapeutic target in herpesvirus-associated chronic diseases. The effects of brincidofovir (BCV) on EBV reactivation were evaluated in vitro using EBV-infected spontaneous lymphoblastoid cell lines (SLCLs) and peripheral blood mononuclear cells (PBMCs) derived from patients with MS and healthy controls. In addition, a B lymphoblastoid cell line and PBMCs from common marmosets (Callithrix jacchus) naturally infected with an EBV-related gammaherpesvirus (Callitrichine herpesvirus 3, CalHV-3) were used to measure BCV efficacy in a nonhuman primate model. BCV significantly inhibited gammaherpesvirus reactivation, with decreased lytic and latent viral transcript expression. These results suggest that BCV may be a useful antiviral for inhibiting EBV activity in patients with MS. Additionally, this work further validates the utility of CalHV-3 in marmosets as a translational model for the investigation of successful EBV-targeting therapeutics.
Authors
- Fuminao Yoshida
- Stacey L. Piotrowski
- Laurie T. Krug (ORCID: https://orcid.org/0000-0002-9648-522X)
- Irene C. M. Cortese (ORCID: https://orcid.org/0000-0001-9631-7181)
- Emily Stack (ORCID: https://orcid.org/0009-0008-0115-7321)
- Peter A. Zimmerman (ORCID: https://orcid.org/0000-0002-5349-4513)
- Heather Lyons Narver
- Steven Jacobson (ORCID: https://orcid.org/0000-0003-3127-1287)
- Ashleigh C. Donaldson (ORCID: https://orcid.org/0000-0003-1586-4744)
- Izabela Bialuk (ORCID: https://orcid.org/0000-0002-4587-8613)
- Maria Chiara Monaco (ORCID: https://orcid.org/0000-0003-0771-0980)
- Xiaofan Li (ORCID: https://orcid.org/0000-0003-4168-0068)
- Amanda J. Lee
- Masatoshi Hazama
- William A. Frazier
- Madeleine R. Druker
Institutions
- National Institutes of Health (US)
- Medical University of Białystok (PL)
- OSE Immunotherapeutics (France) (FR)
- National Institute of Neurological Disorders and Stroke (US)
- National Cancer Institute (US)
- Office of AIDS Research (US)
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2025-11-25
- DOI
- https://doi.org/10.1172/jci195764
- Citations
- 1
- Primary Topic
- Viral-associated cancers and disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.05
Funders
- U.S. Department of Health and Human Services
- Purdue University
- Emory University
- SymBio Pharmaceuticals Limited
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism
- National Institute of Neurological Disorders and Stroke