RhCMV reactivation in SARS-CoV-2 infected aged rhesus macaques
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 hospitaliz...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1616490/full |
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| author | Jamin W. Roh Jamin W. Roh Peter A. Barry Peter W. Hunt Smita S. Iyer Smita S. Iyer Barbara L. Shacklett Barbara L. Shacklett Barbara L. Shacklett |
| author_facet | Jamin W. Roh Jamin W. Roh Peter A. Barry Peter W. Hunt Smita S. Iyer Smita S. Iyer Barbara L. Shacklett Barbara L. Shacklett Barbara L. Shacklett |
| author_sort | Jamin W. Roh |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-75dc611d3f6a4c02bb4b670b941e4e50 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-75dc611d3f6a4c02bb4b670b941e4e502025-08-20T02:21:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16164901616490RhCMV reactivation in SARS-CoV-2 infected aged rhesus macaquesJamin W. Roh0Jamin W. Roh1Peter A. Barry2Peter W. Hunt3Smita S. Iyer4Smita S. Iyer5Barbara L. Shacklett6Barbara L. Shacklett7Barbara L. Shacklett8Graduate Group in Immunology, University of California, Davis, Davis, CA, United StatesDepartment of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, United StatesCalifornia National Primate Research Center, Davis, Davis, CA, United StatesDivision of Experimental Medicine, University of California, San Francisco, San Francisco, CA, United StatesGraduate Group in Immunology, University of California, Davis, Davis, CA, United StatesCalifornia National Primate Research Center, Davis, Davis, CA, United StatesGraduate Group in Immunology, University of California, Davis, Davis, CA, United StatesDepartment of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, United StatesDivision of Infectious Diseases, Department of Medicine, UC Davis School of Medicine, Sacramento, CA, United StatesHuman 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1616490/fullcytomegalovirusrhesus macaqueSARS-CoV-2animal modelsviral reactivation |
| spellingShingle | Jamin W. Roh Jamin W. Roh Peter A. Barry Peter W. Hunt Smita S. Iyer Smita S. Iyer Barbara L. Shacklett Barbara L. Shacklett Barbara L. Shacklett RhCMV reactivation in SARS-CoV-2 infected aged rhesus macaques Frontiers in Immunology cytomegalovirus rhesus macaque SARS-CoV-2 animal models viral reactivation |
| title | RhCMV reactivation in SARS-CoV-2 infected aged rhesus macaques |
| title_full | RhCMV reactivation in SARS-CoV-2 infected aged rhesus macaques |
| title_fullStr | RhCMV reactivation in SARS-CoV-2 infected aged rhesus macaques |
| title_full_unstemmed | RhCMV reactivation in SARS-CoV-2 infected aged rhesus macaques |
| title_short | RhCMV reactivation in SARS-CoV-2 infected aged rhesus macaques |
| title_sort | rhcmv reactivation in sars cov 2 infected aged rhesus macaques |
| topic | cytomegalovirus rhesus macaque SARS-CoV-2 animal models viral reactivation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1616490/full |
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