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Clinical manifestations of HHV infection can range from asymptomatic cases to a broad spectrum of neurological complications, spanning from acute conditions such as encephalitis to chronic disorders including Alzheimer\u2019s disease and multiple sclerosis. By establishing latency and undergoing repeated reactivation, HHVs maintain lifelong interactions with the human immune system and shape host immune responses, exerting considerable impact on nervous system homeostasis. Individual susceptibility to, and outcomes of, HHV-associated neurological disorders depend on multiple factors, including the infecting HHV strain and host genetics. Recent evidence highlights the pivotal role of the human leukocyte antigen E (HLA-E) pathway\u2014a non-classical major histocompatibility complex class I molecule with immunomodulatory functions\u2014in regulating virus\u2013host interactions. Since some HHVs manipulate HLA-E to evade immune recognition, individual variability in this axis may influence neurological outcomes. In this review, we summarize and discuss current knowledge of the role of HLA-E in herpesvirus-associated neurological diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00869-25","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T14:01:34Z","timestamp":1763992894000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Herpesvirus-host interactions in neurological diseases: the immunogenetic role of HLA-E"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2152-7798","authenticated-orcid":false,"given":"Marianne","family":"Graninger","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n3x4p02","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Virology, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-8335","authenticated-orcid":true,"given":"Elisabeth","family":"Puchhammer-St\u00f6ckl","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n3x4p02","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Virology, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3993-6538","authenticated-orcid":true,"given":"Hannes","family":"Vietzen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n3x4p02","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Virology, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"ICTV. 2023 International Committee on the Taxonomy of Viruses 10th Report. 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