{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:09:02Z","timestamp":1778238542743,"version":"3.51.4"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"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":[[2012,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Limited protection of current vaccines and antiviral drugs against influenza A virus infection underscores the urgent need for development of novel anti-influenza virus interventions. While short interfering RNA (siRNA) has been shown to be able to inhibit influenza virus infection in a gene-specific manner, activation of the retinoic acid-inducible gene I protein (RIG-I) pathway has an antiviral effect in a non-gene-specific mode. In this study, we designed and tested the anti-influenza virus effect of a short double-stranded RNA, designated 3p-mNP1496-siRNA, that possesses dual functions: an siRNA-targeting influenza NP gene and an agonist for RIG-I activation. This double-stranded siRNA possesses a triphosphate group at the 5\u2032 end of the sense strand and is blunt ended. Our study showed that 3p-mNP1496-siRNA could potently inhibit influenza A virus infection both in cell culture and in mice. The strong inhibition effect was attributed to its siRNA function as well as its ability to activate the RIG-I pathway. To the best of our knowledge, this is the first report that the combination of siRNA and RIG-I pathway activation can synergistically inhibit influenza A virus infection. The development of such dual functional RNA molecules will greatly contribute to the arsenal of tools to combat not only influenza viruses but also other important viral pathogens.<\/jats:p>","DOI":"10.1128\/jvi.00665-12","type":"journal-article","created":{"date-parts":[[2012,7,12]],"date-time":"2012-07-12T04:53:58Z","timestamp":1342068838000},"page":"10359-10369","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["5\u2032-Triphosphate-Short Interfering RNA: Potent Inhibition of Influenza A Virus Infection by Gene Silencing and RIG-I Activation"],"prefix":"10.1128","volume":"86","author":[{"given":"Li","family":"Lin","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Berube","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Detmer","sequence":"additional","affiliation":[{"name":"Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.24.12925-12933.2002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.18.9225-9231.2002"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.10.032"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35078107"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402486101"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0437841100"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.22.14392-14403.2005"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/104063879100300128"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.08.002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp068030"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0502-500"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06362-11"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1384005"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1205"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.005447-0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168352"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm725"},{"key":"e_1_3_2_19_2","first-page":"1647","volume-title":"Fields virology","author":"Palese P","year":"2007","unstructured":"PaleseP ShawML. 2007. Orthomyxoviridae: the viruses and their replication, p 1647\u20131690. In KnipeDM (ed), Fields virology, 5th ed, vol II. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"5"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.10.020"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0235524100"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-7-102"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.05.008"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900971106"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01427-07"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82483-0"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82419-0"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.11.028"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.11.1333"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402630101"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.11.6298"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.476"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00665-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00665-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T15:16:45Z","timestamp":1646493405000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00665-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10]]},"references-count":31,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1128\/JVI.00665-12"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00665-12","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10]]},"assertion":[{"value":"2012-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-07-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-09-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}