{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:55:41Z","timestamp":1790744141684,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,25]]},"group-title":"Microbiology","reference-count":77,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["AI144492"],"award-info":[{"award-number":["AI144492"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AI185349"],"award-info":[{"award-number":["AI185349"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AG081185"],"award-info":[{"award-number":["AG081185"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NS121727"],"award-info":[{"award-number":["NS121727"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Herpes simplex virus 1 (HSV-1) establishes life-long latency in peripheral neurons following neuroinvasion, yet the early determinants governing latency versus productive infection remain poorly understood. Available\n                  <jats:italic>in vitro<\/jats:italic>\n                  models bypass the physiological route of infection by directly infecting neuronal cell bodies under antiviral suppression. Here, we established a compartmented axonal infection model that recapitulates HSV-1 neuroinvasion and latency establishment without pharmacological inhibitors. Using primary superior cervical ganglion (SCG) neurons, we demonstrated that low-dose axonal infection consistently establishes latency, whereas higher axonal doses or direct somatic infection led to productive replication. Latently infected neurons exhibit accumulation of the latency-associated transcript (LAT) and can be efficiently reactivated by UV-inactivated virus or VP16 expression. Remarkably, productive infection can be induced during low-dose axonal infection by simultaneous exposure of neuronal cell bodies, but not axons, to replication-deficient virions, implicating tegument delivery in soma overrides latency establishment. Conversely, excess replication-incompetent particles in axons suppress productive outcomes and subsequent reactivations, suggesting competition for retrograde transport. Together, these findings identify axonal entry and transport as critical regulatory checkpoints in HSV-1 latency establishment and suggest that interference with retrograde trafficking may represent a strategy to limit neuroinvasion and life-long reactivations.\n                <\/jats:p>","DOI":"10.64898\/2026.09.24.754144","type":"posted-content","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:15:18Z","timestamp":1790392518000},"source":"Crossref","is-referenced-by-count":0,"title":["Axonal entry and retrograde transport define HSV-1 latency establishment and reactivation potential in neurons"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-1412","authenticated-orcid":false,"given":"Christina","family":"Pantoja","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey D.","family":"Loaiza","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khanh T. Y.","family":"Luong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4038-9391","authenticated-orcid":false,"given":"Orkide O.","family":"Koyuncu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092921051166000_2026.09.24.754144v1.1","doi-asserted-by":"publisher","DOI":"10.1136\/sextrans-2024-056307"},{"key":"2026092921051166000_2026.09.24.754144v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140765"},{"key":"2026092921051166000_2026.09.24.754144v1.3","doi-asserted-by":"crossref","unstructured":"D. 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