{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:03:24Z","timestamp":1790327004814,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,12,30]],"date-time":"2017-12-30T00:00:00Z","timestamp":1514592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Type I interferons (IFN-I) are one of the primary immune defenses against viruses. Similar to all other molecular mechanisms that are central to eliciting protective immune responses, IFN-I expression is subject to homeostatic controls that regulate cytokine levels upon clearing the infection. However, in the case of established persistent viral infection, sustained elevation of IFN-I expression bears deleterious effects to the host and is today considered as the major driver of inflammation and immunosuppression. In fact, numerous emerging studies place sustained IFN-I expression as a common nexus in the pathogenesis of multiple chronic diseases including persistent infections with the human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), as well as the rodent-borne lymphocytic choriomeningitis virus clone 13 (LCMV clone 13). In this review, we highlight recent studies illustrating the molecular dysregulation and resultant cellular dysfunction in both innate and adaptive immune responses driven by sustained IFN-I expression. Here, we place particular emphasis on the efficacy of IFN-I receptor (IFNR) blockade towards improving immune responses against viral infections given the emerging therapeutic approach of blocking IFNR using neutralizing antibodies (Abs) in chronically infected patients.<\/jats:p>","DOI":"10.3390\/v10010012","type":"journal-article","created":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T12:00:06Z","timestamp":1514980806000},"page":"12","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Sustained IFN-I Expression during Established Persistent Viral Infection: A \u201cBad Seed\u201d for Protective Immunity"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3004-849X","authenticated-orcid":false,"given":"Xavier","family":"Dagenais-Lussier","sequence":"first","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, H7V 1B7 QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2646-524X","authenticated-orcid":false,"given":"Hamza","family":"Loucif","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, H7V 1B7 QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armstrong","family":"Murira","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, H7V 1B7 QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Laulh\u00e9","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, H7V 1B7 QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"St\u00e4ger","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, H7V 1B7 QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Lamarre","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, H7V 1B7 QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Van Grevenynghe","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, H7V 1B7 QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.cytogfr.2014.10.004","article-title":"Type I IFN\u2014A blunt spear in fighting HIV-1 infection","volume":"26","author":"Acchioni","year":"2015","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nrd2422","article-title":"Interferons at age 50: Past, current and future impact on biomedicine","volume":"6","author":"Borden","year":"2007","journal-title":"Nat. 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