ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1616490
RhCMV reactivation in SARS-CoV-2 infected aged rhesus macaques
Provisionally accepted
- 1Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States
- 2California National Primate Research Center, University of California, Davis, Davis, California, United States
- 3Division of Experimental Medicine, Department of Medicine, School of Medicine, University of California San Francisco, San Francisco, United States
- 4Division of Experimental Pathology, Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- 5Division of Infectious Diseases, Department of Internal Medicine, School of Medicine, University of California, Davis, Davis, California, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Human Cytomegalovirus (HCMV) is a ubiquitous virus with a global prevalence of 90%, but infection typically has minimal clinical impact in immunocompetent individuals. Consequently, most people are neither tested nor treated for HCMV. However, HCMV seropositivity is associated with higher hospitalization rates following SARS-CoV-2 infection compared to seronegative individuals, suggesting that viral reactivation may exacerbate severity of clinical symptoms. To investigate this, rhesus macaques naturally infected with rhesus cytomegalovirus (RhCMV) were experimentally inoculated with SARS-CoV-2 and monitored. Following inoculation, RhCMV viral loads in plasma increased from baseline, indicating reactivation. Within tissues, the lungs and ileum expressed immediate early protein-1 (IE1), a marker of active RhCMV infection.Additionally, elevated frequencies of circulating activated CD69 + memory T cells at day 3 suggested a recall response to a previously encountered pathogen. These findings demonstrate RhCMV reactivation and associated immune activation following SARS-CoV-2 infection, highlighting the rhesus macaque/RhCMV model as a valuable tool to elucidate the role of HCMV in SARS-CoV2 disease in immunocompetent hosts.
Keywords: Cytomegalovirus, rhesus macaque, SARS-CoV-2, Animal Models, Viral reactivation
Received: 22 Apr 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Roh, Barry, Hunt, Iyer and Shacklett. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Smita S Iyer, Division of Experimental Pathology, Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, Pennsylvania, United States
Barbara L Shacklett, Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, 95616, California, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.