{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:30:42Z","timestamp":1786516242585,"version":"build-2736575974"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY036253, R01EY029426, R01EY033622, R01EY024710, P30EY001792"],"award-info":[{"award-number":["R01EY036253, R01EY029426, R01EY033622, R01EY024710, P30EY001792"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Akt1 and Akt2 isoforms reveal distinct immune-regulatory roles in HSV-1 pathogenesis. Akt3 is a developmentally important protein, and mutations in Akt3 gene are associated with a wide spectrum of developmental disorders, including extreme megalencephaly; however, its role in corneal homeostasis and pathologies remains poorly understood. Here we investigated the role of Akt3 in HSV-1 infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vivo<\/jats:italic>\n                      HSV-1 infection was performed using WT, Akt3 homozygous, and heterozygous mutant mice via corneal scarification to assess disease outcomes. Viral replication was quantified by plaque assays from ocular samples at defined time points. Mice were subjected to ex vivo and\n                      <jats:italic>in vitro<\/jats:italic>\n                      analyses, including flow cytometry, ELISA, and neutralization assays, to comprehensively evaluate innate and adaptive immune responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, we report the significance of the Akt3 isoform in HSV-1 viral pathogenesis. Loss of Akt3 at baseline results in spontaneous corneal opacity, suggesting it is a critical regulator of ocular homeostasis. Despite this baseline compromise, Akt3 deficient mice appear to be better protected against HSV-1 infection, showing lower titers and better survivability. Loss of Akt3 plays a unique role in regulating type 1 interferon production necessary for combating viral infection, along with demonstrating significantly higher serum neutralizing capacity compared to WT controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Akt3 deficiency reconfigures the innate-adaptive interface acting as a negative modulator of the antiviral response during HSV-1 infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1847233","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:55:27Z","timestamp":1786514127000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of Akt3 enhances antiviral immunity while disrupting corneal homeostasis during ocular HSV-1 infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Rashmi","family":"Kadam","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois Chicago","place":["Chicago, IL, United States"]},{"name":"Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois Chicago","place":["Chicago, IL, United States"]},{"name":"Department of Immunology and Microbiology, College of Medicine, University of Illinois Chicago","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrashekhar D.","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois Chicago","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemant","family":"Borase","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois Chicago","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Rahangdale","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois Chicago","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ipsita","family":"Volety","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois Chicago","place":["Chicago, IL, United States"]},{"name":"Department of Pathology, College of Medicine, University of Illinois Chicago","place":["Chicago, IL, United 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