{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:45:57Z","timestamp":1760150757199,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T00:00:00Z","timestamp":1703548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Changchun Science and Technology Development Plan Project","award":["21ZGY30","2020-12M-5-001"],"award-info":[{"award-number":["21ZGY30","2020-12M-5-001"]}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["21ZGY30","2020-12M-5-001"],"award-info":[{"award-number":["21ZGY30","2020-12M-5-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>SARS-CoV-2 triggered the global COVID-19 pandemic, posing a severe threat to public health worldwide. The innate immune response in cells infected by SARS-CoV-2 is primarily orchestrated by type I interferon (IFN), with IFN-\u03b2 exhibiting a notable inhibitory impact on SARS-CoV-2 replication. FHL2, acting as a docking site, facilitates the assembly of multiprotein complexes and regulates the transcription of diverse genes. However, the association between SARS-CoV-2 and FHL2 remains unclear. In this study, we report for the first time that SARS-CoV-2 infection in Caco2 cells results in the upregulation of FHL2 expression, while the virus\u2019s N proteins can enhance FHL2 expression. Notably, the knockdown of FHL2 significantly amplifies SARS-CoV-2 replication in vitro. Conversely, the overexpression of FHL2 leads to a marked reduction in SARS-CoV-2 replication, with the antiviral property of FHL2 being independent of the cell or virus type. Subsequent experiments reveal that FHL2 supports IFN-\u03b2 transcription by upregulating the expression and phosphorylation of IRF-3, thereby impeding SARS-CoV-2 replication in cells. These findings highlight FHL2 as a potential antiviral target for treating SARS-CoV-2 infections.<\/jats:p>","DOI":"10.3390\/ijms25010353","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T02:58:12Z","timestamp":1703645892000},"page":"353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FHL2 Inhibits SARS-CoV-2 Replication by Enhancing IFN-\u03b2 Expression through Regulating IRF-3"],"prefix":"10.3390","volume":"25","author":[{"given":"Zhiqiang","family":"Xu","sequence":"first","affiliation":[{"name":"Agricultural College, Yanbian University, Yanji 133002, China"},{"name":"Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyao","family":"Tian","sequence":"additional","affiliation":[{"name":"Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihan","family":"Tan","sequence":"additional","affiliation":[{"name":"Agricultural College, Yanbian University, Yanji 133002, China"},{"name":"Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Hao","sequence":"additional","affiliation":[{"name":"Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihan","family":"Gao","sequence":"additional","affiliation":[{"name":"Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3267-1859","authenticated-orcid":false,"given":"Chang","family":"Li","sequence":"additional","affiliation":[{"name":"Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningyi","family":"Jin","sequence":"additional","affiliation":[{"name":"Agricultural College, Yanbian University, Yanji 133002, China"},{"name":"Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41564-020-0695-z","article-title":"The species Severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2","volume":"5","author":"Gorbalenya","year":"2020","journal-title":"Nat. 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