{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:48Z","timestamp":1787027868455,"version":"build-2736575974"},"reference-count":142,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinics and Practice"],"abstract":"<jats:p>Background: Herpes simplex virus (HSV), Epstein\u2013Barr virus (EBV), and cytomegalovirus (CMV) establish lifelong latency in sensory neurons, lymphoid tissue, and myeloid\u2013endothelial cells, respectively. A substantial proportion of adults worldwide are infected with all three viruses and may experience concurrent herpesvirus latency, yet they have largely been studied independently. This review examined whether latent and intermittently reactivating herpesviruses share overlapping inflammatory signatures and whether their combined presence contributes to chronic inflammatory burden. Methods: A narrative integrative review was conducted using MEDLINE, Embase, and Google Scholar (inception\u2013October 2025). Evidence from thirty-one cohort studies and mechanistic investigations spanning virology, immunology, neurology, and clinical medicine was synthesized. Results: Herpesvirus reactivation rates ranged from 23% in general Intensive Care Unit (ICU) populations to 85% in severe COVID-19. Concurrent reactivation of multiple viruses occurred in 34\u201363% of critically ill patients and was associated with worse clinical outcomes. Notably, simultaneous CMV and EBV reactivation independently predicted mortality (adjusted hazard ratio, 3.17; 95% CI, 1.41\u20137.13). Across infections, overlapping inflammatory biomarkers, including IL-6, TNF-\u03b1, CRP, and PGE2, were consistently elevated, reflecting convergent activation of IFN and NF-\u03baB signaling pathways. Mechanistic studies suggest cross-compartment immune priming, where CMV-driven T-cell exhaustion facilitates EBV reactivation, and viral cytokine signaling enhances HSV-associated neuroinflammation. Conclusions: HSV, EBV, and CMV triple latency may represent an underrecognized contributor to chronic inflammation in immunocompetent hosts. Understanding this multi-virus inflammatory network may inform mechanistic research, biomarker-guided risk stratification, and therapeutic strategies targeting convergent inflammatory pathways. Prospective interventional studies incorporating concurrent multi-virus monitoring are needed to clarify causal relationships.<\/jats:p>","DOI":"10.3390\/clinpract16040064","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:05:49Z","timestamp":1775563549000},"page":"64","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Triple Latency as a Driver of Chronic Inflammation: An Integrative View of HSV, EBV, and CMV Persistence in Immunocompetent Hosts"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4976-5333","authenticated-orcid":false,"given":"Maria E.","family":"Ramos-Nino","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Pharmacology, St. George\u2019s University School of Medicine, St. George P.O. Box 7, Grenada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.2174\/1570159X22666231017141636","article-title":"Inflammation, Autoimmunity and Neurodegenerative Diseases, Therapeutics and Beyond","volume":"22","author":"Garmendia","year":"2024","journal-title":"Curr. Neuropharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, Y., Molleston, J.M., Lovato, C., Wright, J., Erickson, I., Bui, D., Kim, A.H., Ingle, H., Aggarwal, S., and Nolan, L.S. (2024). Sequential Early-Life Viral Infections Modulate the Microbiota and Adaptive Immune Responses to Systemic and Mucosal Vaccination. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012557"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Forte, E., Zhang, Z., Thorp, E.B., and Hummel, M. (2020). 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