{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T21:29:02Z","timestamp":1783978142839,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chronic hepatitis B (CHB) is a widespread form of hepatitis B infection with advanced complications if unsupervised and untreated. It was previously reported that pregenomic RNA (pgRNA) can be detected in blood circulation as an indirect marker of HBV transcriptional activity. The aim of this study was to investigate the transcriptomic profile of pgRNA-positive patients with CHB in comparison to pgRNA-negative patients and to evaluate its role in innate immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A total of 88 patients with CHB who were receiving nucleoside analogs (NAs) were enrolled in this study. The viral load and genotype, HBV pgRNA, and biochemical and virological markers were determined. Samples from eight CHB HBeAg-negative patients were sequenced. Four of them were positive for HBV pgRNA, while the rest were negative. These data were processed via bioinformatic tools. Bioinformatic analyses revealed common pathways such as platelet activation and neutrophil degranulation, for which experimental setups were organized. Platelet activation, as well as platelet\u2013neutrophil interactions, was examined. Furthermore, the synthesis and expression of interleukins IL-1\u03b2, IL-17A, and LL-37 were studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The percentage of patients positive for HBV pgRNA in the study population was 18.1%. With respect to the transcriptomic analysis, which was performed via two distinct analyses, we identified common differentially expressed (DE) genes involved in platelet activation and neutrophil degranulation pathways. Afterwards, the induction of autophagy in platelets and the\n                      <jats:italic>de novo<\/jats:italic>\n                      synthesis of the peptide LL-37 were observed in platelets stimulated with HBV pgRNA-positive serum. Furthermore, a combined study of platelet\u2013neutrophil interactions revealed the development of a proinflammatory phenotype characterized by high levels of IL-1\u03b2 in neutrophils, accompanied by minimal NET formation. In conclusion, those findings were intended to demonstrate the overexpression of IL-1\u03b2 and LL-37 in the liver tissue of patients with CHB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrated that HBV pgRNA activates platelets in an autophagy-dependent manner. Moreover, the platelet\u2013neutrophil axis is responsible for a proinflammatory phenotype in which IL-1\u03b2 is overexpressed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1812831","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:38:20Z","timestamp":1782103100000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["HBV pgRNA induces chronic inflammation in an IL-1\u03b2-dependent manner"],"prefix":"10.3389","volume":"17","author":[{"given":"Aikaterini","family":"Skeva","sequence":"first","affiliation":[{"name":"Laboratory of Microbiology, Department of Medicine, School of Health Sciences, Democritus University of Thrace","place":["Alexandroupolis, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Marmanis","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, 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