{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:48:21Z","timestamp":1786978101642,"version":"build-2736575974"},"reference-count":78,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Herpes simplex virus type 1 (HSV\u20101), a ubiquitous neurotropic virus, has been increasingly associated with neurodegenerative disorders through mechanisms extending beyond acute encephalitis to include chronic neuroinflammation, proteostatic disruption, and immune dysregulation. Simultaneously, the gut\u2010brain\u2010immune axis has gained recognition as a master regulator of central nervous system (CNS) homeostasis. In this review, we delineate how HSV\u20101 neurovirulence intersects with gut microbiota dynamics and immune signaling to shape neuropathological trajectories. We explore five interconnected domains: the gut\u2013brain axis as a mediator of systemic inflammation and neurodegeneration in HSV\u20101 infection; the influence of gut microbial metabolites on blood\u2010brain barrier (BBB) integrity and immune cell trafficking; microbiota\u2010dependent modulation of microglial activation during HSV\u20101\u2010induced neuroinflammation; gut\u2013microbiota regulation of proteostasis under viral stress; and therapeutic strategies targeting the microbiota to attenuate HSV\u20101\u2010associated cognitive decline. We synthesize multidisciplinary evidence demonstrating that microbial dysbiosis exacerbates neuroimmune dysfunction, while microbiota\u2010derived signals, such as short\u2010chain fatty acids (SCFAs), tryptophan catabolites, and postbiotics, exert protective effects by reinforcing barrier integrity, regulating glial responses, and restoring proteostatic balance. Finally, we advocate for integrative therapeutic approaches that combine antiviral interventions with microbiota\u2010based strategies, offering a conceptual framework for precision neuroimmunology in viral encephalopathies. This study repositions HSV\u20101 not merely as a latent pathogen but as a dynamic instigator of neurodegeneration within a vulnerable host\u2010microbe ecosystem.<\/jats:p>","DOI":"10.1002\/jmv.70504","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T10:47:42Z","timestamp":1753354062000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Unraveling the Gut\u2010Brain\u2010Immune Interplay in Herpes Simplex Virus\u2010Associated Neurodegeneration"],"prefix":"10.1002","volume":"97","author":[{"given":"Jhommara","family":"Bautista","sequence":"first","affiliation":[{"name":"Cancer Research Group (CRG), Faculty of Medicine Universidad de Las Am\u00e9ricas Quito Ecuador"},{"name":"Facultade de Ciencias, Campus de A Zapateira Universidade da Coru\u00f1a A Coru\u00f1a 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