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One key marker of AD is the hyperphosphorylation of Tau, accompanied by altered levels of Tau isoforms. However, an imbalance in these Tau splice variants, specifically resulting from altered 3R to 4R <jats:italic>MAPT<\/jats:italic> splicing of exon 10, has yet to be directly associated with HSV\u20101 infection. To this end, we infected 2D and 3D human neural models with HSV\u20101 and monitored <jats:italic>MAPT<\/jats:italic> splicing and Tau phosphorylation. Further, we transduced SH\u2010SY5Y neurons with HSV\u20101 ICP27, which alters RNA splicing, to analyze if ICP27 alone is sufficient to induce altered <jats:italic>MAPT<\/jats:italic> exon 10 splicing. We show that HSV\u20101 infection induces altered splicing of <jats:italic>MAPT<\/jats:italic> exon 10, increasing 4R\u2010Tau protein levels, Tau hyperphosphorylation, and Tau oligomerization. Our experiments reveal a novel link between HSV\u20101 infection and the development of cytopathic phenotypes linked with AD progression.<\/jats:p>","DOI":"10.1111\/bpa.70006","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T15:30:54Z","timestamp":1743262254000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Herpes simplex virus\u20101 infection alters microtubule\u2010associated protein <scp>Tau<\/scp> splicing and promotes <scp>Tau<\/scp> pathology in neural models of <scp>Alzheimer's<\/scp> disease"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1127-0367","authenticated-orcid":false,"given":"Emmanuel C.","family":"Ijezie","sequence":"first","affiliation":[{"name":"Microbiology and Immunology Department SUNY Upstate Medical University  Syracuse New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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