Publications

Journal Article Epublish

PubMed: 40630948 DOI: 10.3389/fimmu.2025.1616490

RhCMV reactivation in SARS-CoV-2 infected aged rhesus macaques.

Front Immunol 16:1616490

Authors: Jamin W Roh, Peter A Barry, Peter W Hunt, Smita S Iyer, Barbara L Shacklett

Affiliations

  • Graduate Group in Immunology, University of California, Davis, Davis, CA, United States.
  • Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, United States.
  • California National Primate Research Center, Davis, Davis, CA, United States.
  • Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, United States.
  • Division of Infectious Diseases, Department of Medicine, UC Davis School of Medicine, Sacramento, CA, United States.

Abstract

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.

MeSH

Sars-Cov-2, Cytomegalovirus, Signs And Symptoms, Aged, Viruses, Severe Acute Respiratory Syndrome-Related Coronavirus, Infections