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After primary lytic replication in the oral, ocular, and nasal mucosal epithelial cells, HSV-1 establishes life-long latency in neurons within the trigeminal ganglion. Patients with compromised immune systems experience frequent reactivation of HSV-1 from latency, leading to virus entry in the sensory neurons, followed by anterograde transport and lytic replication at the innervated mucosal epithelial surface. Although recurrent infection of the corneal mucosal surface is rare, it can result in a chronic immuno-inflammatory condition called herpetic stromal keratitis (HSK). HSK leads to gradual vision loss and can cause permanent blindness in severe untreated cases. Currently, there is no cure or successful vaccine to prevent latent or recurrent HSV-1 infections, posing a significant clinical challenge to managing HSK and preventing vision loss. The conventional clinical management of HSK primarily relies on anti-virals to suppress HSV-1 replication, anti-inflammatory drugs (such as corticosteroids) to provide symptomatic relief from pain and inflammation, and surgical interventions in more severe cases to replace damaged cornea. However, each clinical treatment strategy has limitations, such as local and systemic drug toxicities and the emergence of anti-viral-resistant HSV-1 strains. In this review, we summarize the factors and immune cells involved in HSK pathogenesis and highlight alternate therapeutic strategies for successful clinical management of HSK. We also discuss the therapeutic potential of immunoregulatory cytokines and immunometabolism modulators as promising HSK therapies against emerging anti-viral-resistant HSV-1 strains.<\/jats:p>","DOI":"10.1128\/cmr.00006-24","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T09:00:20Z","timestamp":1722330020000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":52,"title":["The immunobiology of corneal HSV-1 infection and herpetic stromal keratitis"],"prefix":"10.1128","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9269-3614","authenticated-orcid":false,"given":"Ferrin","family":"Antony","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6848-2525","authenticated-orcid":false,"given":"Divya","family":"Kinha","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Nowi\u0144ska","sequence":"additional","affiliation":[{"name":"Clinical Department of Ophthalmology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Katowice, Poland"},{"name":"Ophthalmology Department, Railway Hospital in Katowice, Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8829-0334","authenticated-orcid":false,"given":"Barry T.","family":"Rouse","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5031-5818","authenticated-orcid":false,"given":"Amol","family":"Suryawanshi","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801238-3.00080-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-53168-7_6"},{"key":"e_1_3_2_4_2","first-page":"310","article-title":"A nurse practitioner\u2019s guide to the management of herpes simplex virus-1 in children","volume":"34","author":"Drugge JM","year":"2008","unstructured":"Drugge JM, Allen PJ. 2008. 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