{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:08:58Z","timestamp":1789682938648,"version":"4.0.1"},"reference-count":47,"publisher":"Microbiology Society","issue":"10","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007271","name":"Health Science Center, University of Tennessee","doi-asserted-by":"crossref","award":["College of Medicine Research Incentive Funds"],"award-info":[{"award-number":["College of Medicine Research Incentive Funds"]}],"id":[{"id":"10.13039\/100007271","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,31]]},"abstract":"<jats:p>\n                    Laboratory of genetics and physiology 2 (LGP2, also known as DHX58) is unique among members of the RIG-I-like receptor (RLR) family as it lacks the caspase activation and recruitment domain. Although LGP2 per se cannot directly activate downstream antiviral signalling, it plays important regulatory roles, primarily by modulating innate immune responses mediated by RIG-I and MDA5. However, the detailed mechanisms by which LGP2 is induced in mammalian cells during viral infection remain incompletely understood. Herein, we show that LGP2 is strongly upregulated by dsRNA stimulation or virus infection in cultured human cell lines via TLR3 and RLRs, respectively, and that substantial induction of LGP2 remains when paracrine\/autocrine signalling of IFNs and\/or inflammatory cytokines is abrogated by genetic deletion or chemical inhibition. The latter observation is in stark contrast to the case of myxovirus resistance proteins, the induction of which is strictly IFN-dependent. Mechanistically, we found LGP2 expression to be upregulated by ectopic expression of IRF3-5D, a phospho-mimetic mutant of activated IRF3, or to a lesser extent, by overexpression of RELA, the p65 subunit of NF\u03baB, in an IFN-independent fashion. Additionally, we demonstrated that this regulation operated transcriptionally at the\n                    <jats:italic>LGP2<\/jats:italic>\n                    promoter level. Altogether, a fraction of LGP2 induction in viral infection is IFN- and cytokine-independent, highlighting exquisite gene expression control in antiviral innate immunity and representing an evolutionary advantage, which ensures uninterrupted supply of this RLR member protein in host responses to invading viruses in the event that IFN production and\/or signalling is disabled by viral means.\n                  <\/jats:p>","DOI":"10.1099\/jgv.0.002173","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T17:17:15Z","timestamp":1761931035000},"source":"Crossref","is-referenced-by-count":4,"title":["Cytokine-independent induction of LGP2\/DHX58 in viral infection"],"prefix":"10.1099","volume":"106","author":[{"given":"Yaxin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, PR China"},{"name":"Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN 38163, USA"},{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z. 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