{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:11:53Z","timestamp":1789441913733,"version":"build-2803163510"},"reference-count":168,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heinz-Ansmann Foundation for AIDS Research","award":["318346496"],"award-info":[{"award-number":["318346496"]}]},{"name":"Heinz-Ansmann Foundation for AIDS Research","award":["SPP1923"],"award-info":[{"award-number":["SPP1923"]}]},{"name":"Heinz-Ansmann Foundation for AIDS Research","award":["202008080281"],"award-info":[{"award-number":["202008080281"]}]},{"name":"Heinz-Ansmann Foundation for AIDS Research","award":["202308520034"],"award-info":[{"award-number":["202308520034"]}]},{"name":"German Research Foundation","award":["318346496"],"award-info":[{"award-number":["318346496"]}]},{"name":"German Research Foundation","award":["SPP1923"],"award-info":[{"award-number":["SPP1923"]}]},{"name":"German Research Foundation","award":["202008080281"],"award-info":[{"award-number":["202008080281"]}]},{"name":"German Research Foundation","award":["202308520034"],"award-info":[{"award-number":["202308520034"]}]},{"name":"China Scholarship Council","award":["318346496"],"award-info":[{"award-number":["318346496"]}]},{"name":"China Scholarship Council","award":["SPP1923"],"award-info":[{"award-number":["SPP1923"]}]},{"name":"China Scholarship Council","award":["202008080281"],"award-info":[{"award-number":["202008080281"]}]},{"name":"China Scholarship Council","award":["202308520034"],"award-info":[{"award-number":["202308520034"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The innate immune response to viruses is formed in part by interferon (IFN)-induced restriction factors, including ISG15, p21, and SAMHD1. IFN production can be blocked by the ISG15-specific protease USP18. HIV-1 has evolved to circumvent host immune surveillance. This mechanism might involve USP18. In our recent studies, we demonstrate that HIV-1 infection induces USP18, which dramatically enhances HIV-1 replication by abrogating the antiviral function of p21. USP18 downregulates p21 by accumulating misfolded dominant negative p53, which inactivates wild-type p53 transactivation, leading to the upregulation of key enzymes involved in de novo dNTP biosynthesis pathways and inactivated SAMHD1. Despite the USP18-mediated increase in HIV-1 DNA in infected cells, it is intriguing to note that the cGAS-STING-mediated sensing of the viral DNA is abrogated. Indeed, the expression of USP18 or knockout of ISG15 inhibits the sensing of HIV-1. We demonstrate that STING is ISGylated at residues K224, K236, K289, K347, K338, and K370. The inhibition of STING K289-linked ISGylation suppresses its oligomerization and IFN induction. We propose that human USP18 is a novel factor that potentially contributes in multiple ways to HIV-1 replication.<\/jats:p>","DOI":"10.3390\/v16040485","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T05:10:53Z","timestamp":1711084253000},"page":"485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The ISG15-Protease USP18 Is a Pleiotropic Enhancer of HIV-1 Replication"],"prefix":"10.3390","volume":"16","author":[{"given":"Chaohui","family":"Lin","sequence":"first","affiliation":[{"name":"Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund Osei","family":"Kuffour","sequence":"additional","affiliation":[{"name":"Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taolan","family":"Li","sequence":"additional","affiliation":[{"name":"Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph G. W.","family":"Gertzen","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-0911","authenticated-orcid":false,"given":"Jesko","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6288-8821","authenticated-orcid":false,"given":"Tom","family":"Luedde","sequence":"additional","affiliation":[{"name":"Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4882-9179","authenticated-orcid":false,"given":"Renate","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions, Paul-Ehrlich-Institut, 63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8613-1447","authenticated-orcid":false,"given":"Holger","family":"Gohlke","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Institute of Bio- and Geosciences (IBG-4: Bioinformatics), Forschungszentrum J\u00fclich GmbH, 52425 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-9311","authenticated-orcid":false,"given":"Carsten","family":"M\u00fcnk","sequence":"additional","affiliation":[{"name":"Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a012526","DOI":"10.1101\/cshperspect.a012526","article-title":"HIV pathogenesis: Dynamics and genetics of viral populations and infected cells","volume":"3","author":"Coffin","year":"2013","journal-title":"Cold Spring Harb. 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