{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:05:03Z","timestamp":1785423903068,"version":"3.56.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"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>Hepatitis E virus (HEV) is relevant to public health worldwide, and it affects a variety of animals. Big liver and spleen disease (BLS) and hepatitis-splenomegaly syndrome (HSS) associated with avian HEV (aHEV) were first reported in 1988 and in 1991, respectively. Here, cell culture\u2013adapted aHEV genotype 3 strain, YT-aHEV (YT strain), a typical genotype isolated in China, was used for basic and applied research. We evaluated liver injury during the early stages of infection caused by the YT strain <jats:italic>in vivo<\/jats:italic>. Both <jats:italic>in vivo and in vitro<\/jats:italic> experimental data demonstrated that viral infection induces innate immunity, with mRNA expression levels of two key inflammatory factors, interleukin-1\u03b2 (IL-1\u03b2) and IL-18, significantly upregulated. The YT strain infection was associated with the activation of Toll-like receptors (TLRs), nuclear factor kappa B (NF-\u03baB), caspase-1, and NOD-like receptors (NLRs) in the liver and primary hepatocellular carcinoma epithelial cells (LMH). Moreover, inhibiting c-Jun N-terminal kinase, extracellular signal\u2013regulated kinase (ERK1 or 2), P38, NF-\u03baB, or caspase-1 activity has different effects on NLRs, and there is a mutual regulatory relationship between these signaling pathways. The results show that SB 203580, U0126, and VX-765 inhibited IL-1\u03b2 and IL-18 induced by the YT strain, whereas Pyrrolidinedithiocarbamate (PDTC) had no significant effect on the activity of IL-1\u03b2 and IL-18. Pretreatment of cells with SP600125 had an inhibitory effect on IL-18 but not on IL-1\u03b2. The analysis of inhibition results suggests that there is a connection between Mitogen-activated protein kinase (MAPK), NF-\u03baB, and the NLRs signaling pathways. This study explains the relationship between signaling pathway activation (TLRs, NF-\u03baB, MAPK, and NLR\u2013caspase-1) and viral-associated inflammation caused by YT strain infection, which will help to dynamic interaction between aHEV and host innate immunity.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1161665","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T12:37:29Z","timestamp":1680179849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Inflammatory response triggered by avian hepatitis E virus in vivo and in 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