{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:36:48Z","timestamp":1791992208993,"version":"4.4.0"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2014,4,15]],"date-time":"2014-04-15T00:00:00Z","timestamp":1397520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    RIG-I is a cytosolic sensor critically involved in the activation of the innate immune response to RNA virus infection. In the present study, we evaluated the inhibitory effect of a RIG-I agonist on the replication of two emerging arthropod-borne viral pathogens, dengue virus (DENV) and chikungunya virus (CHIKV), for which no therapeutic options currently exist. We demonstrate that when a low, noncytotoxic dose of an optimized 5\u2032triphosphorylated RNA (5\u2032pppRNA) molecule was administered, RIG-I stimulation generated a robust antiviral response against these two viruses. Strikingly, 5\u2032pppRNA treatment before or after challenge with DENV or CHIKV provided protection against infection. In primary human monocytes and monocyte-derived dendritic cells, the RIG-I agonist blocked both primary infection and antibody-dependent enhancement of DENV infection. The protective response against DENV and CHIKV induced by 5\u2032pppRNA was dependent on an intact RIG-I\/MAVS\/TBK1\/IRF3 axis and was largely independent of the type I IFN response. Altogether, this\n                    <jats:italic>in vitro<\/jats:italic>\n                    analysis of the antiviral efficacy of 5\u2032pppRNA highlights the therapeutic potential of RIG-I agonists against emerging viruses such as DENV and CHIKV.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    DENV and CHIKV are two reemerging mosquito-borne viruses for which no therapeutic options currently exist. Both viruses overlap geographically in tropical regions of the world, produce similar fever-like symptoms, and are difficult to diagnose. This study investigated the inhibitory effect of a RIG-I agonist on the replication of these two viruses. RIG-I stimulation using 5\u2032pppRNA before or after DENV or CHIKV infection generated a protective antiviral response against both pathogens in immune and nonimmune cells; interestingly, the protective response against the viruses was largely independent of the classical type I interferon response. The antiviral efficacy of 5\u2032pppRNA highlights the therapeutic potential of RIG-I agonists against emerging viruses such as DENV and CHIKV.\n                  <\/jats:p>","DOI":"10.1128\/jvi.03114-13","type":"journal-article","created":{"date-parts":[[2014,1,29]],"date-time":"2014-01-29T23:17:19Z","timestamp":1391037439000},"page":"4180-4194","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":130,"title":["Inhibition of Dengue and Chikungunya Virus Infections by RIG-I-Mediated Type I Interferon-Independent Stimulation of the Innate Antiviral Response"],"prefix":"10.1128","volume":"88","author":[{"given":"David","family":"Olagnier","sequence":"first","affiliation":[{"name":"Vaccine &amp; Gene Therapy Institute of Florida, Port St. Lucie, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florine E. M.","family":"Scholte","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Chiang","sequence":"additional","affiliation":[{"name":"Vaccine &amp; Gene Therapy Institute of Florida, Port St. Lucie, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina C.","family":"Albulescu","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Nichols","sequence":"additional","affiliation":[{"name":"Vaccine &amp; Gene Therapy Institute of Florida, Port St. Lucie, Florida, 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