{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:07:06Z","timestamp":1789103226581,"version":"build-2803163510"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The cGAS-STING signaling axis constitutes a pivotal defense mechanism in innate immunity, where the second messenger cyclic 2\u2019, 3\u2019-GMP-AMP (hereafter referred to as cGAMP) orchestrates the induction of type I interferons (IFNs) to combat viral infections. Despite its therapeutic potential, the clinical translation of cGAMP is severely hampered by its intrinsic physicochemical properties\u2014high hydrophilicity and polyanionic charge\u2014which result in poor membrane permeability and suboptimal bioavailability. Here, we identify Pt5-1c, a zebrafish phosvitin-derived antimicrobial peptide, as a potent immunomodulatory agent that overcomes this delivery bottleneck. Our results demonstrate that Pt5-1c significantly amplifies cGAMP-mediated immune signaling by enhancing its extracellular availability. Mechanistically, Microscale Thermophoresis (MST) and LC-MS\/MS analyses reveal that Pt5-1c directly complexes with cGAMP, facilitating its efficient delivery to target cells, thereby triggering a robust STING-dependent cascade and downstream effector expression. In both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    models, the Pt5-1c\/cGAMP synergy elicited a superior interferon response and conferred profound protection against virus challenges. This study not only uncovers a novel functional role for antimicrobial peptides as facilitators of intracellular signaling but also provides a strategic framework for the development of next-generation STING-targeted antiviral immunotherapies.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1909072","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:34:47Z","timestamp":1789101287000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Antimicrobial peptide Pt5-1c exerts potent immunomodulatory and antiviral effects by facilitating cellular delivery of cGAMP"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuelian","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zetao","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuran","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University","place":["Beijing, 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