{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:45:27Z","timestamp":1790693127786,"version":"4.1.0"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T00:00:00Z","timestamp":1450137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2015,12,31]],"date-time":"2015-12-31T00:00:00Z","timestamp":1451520000000},"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":["mBio"],"published-print":{"date-parts":[[2015,12,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Dengue virus is a major human pathogen responsible for 400 million infections yearly. As with other RNA viruses, daunting challenges to antiviral design exist due to the high error rates of RNA-dependent RNA synthesis. Indeed, treatment of dengue virus infection with a nucleoside analog resulted in the expected genetic selection of resistant viruses in tissue culture and in mice. However, when the function of the oligomeric core protein was inhibited, no detectable selection of drug resistance in tissue culture or in mice was detected, despite the presence of drug-resistant variants in the population. Suppressed selection of drug-resistant virus correlated with cooligomerization of the targeted drug-susceptible and drug-resistant core proteins. The concept of \u201cdominant drug targets,\u201d in which inhibition of oligomeric viral assemblages leads to the formation of drug-susceptible chimeras, can therefore be used to prevent the outgrowth of drug resistance during dengue virus infection.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Drug resistance is a major hurdle in the development of effective antivirals, especially those directed at RNA viruses. We have found that one can use the concept of the genetic dominance of defective subunits to \u201cturn cousins into enemies,\u201d i.e., to thwart the outgrowth of drug-resistant viral genomes as soon as they are generated. This requires deliberate targeting of larger assemblages, which would otherwise rarely be considered by antiviral researchers.\n          <\/jats:p>","DOI":"10.1128\/mbio.01960-15","type":"journal-article","created":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T02:03:46Z","timestamp":1450231426000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Suppression of Drug Resistance in Dengue Virus"],"prefix":"10.1128","volume":"6","author":[{"given":"Roberto","family":"Mateo","sequence":"first","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, California, USA"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude M.","family":"Nagamine","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, 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