{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:32:01Z","timestamp":1790785921859,"version":"4.1.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:00:00Z","timestamp":1272672000000},"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":[[2010,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In retroviruses and the double-stranded RNA totiviruses, the efficiency of programmed \u22121 ribosomal frameshifting is critical for ensuring the proper ratios of upstream-encoded capsid proteins to downstream-encoded replicase enzymes. The genomic organizations of many other frameshifting viruses, including the coronaviruses, are very different, in that their upstream open reading frames encode nonstructural proteins, the frameshift-dependent downstream open reading frames encode enzymes involved in transcription and replication, and their structural proteins are encoded by subgenomic mRNAs. The biological significance of frameshifting efficiency and how the relative ratios of proteins encoded by the upstream and downstream open reading frames affect virus propagation has not been explored before. Here, three different strategies were employed to test the hypothesis that the \u22121 PRF signals of coronaviruses have evolved to produce the correct ratios of upstream- to downstream-encoded proteins. Specifically, infectious clones of the severe acute respiratory syndrome (SARS)-associated coronavirus harboring mutations that lower frameshift efficiency decreased infectivity by &gt;4 orders of magnitude. Second, a series of frameshift-promoting mRNA pseudoknot mutants was employed to demonstrate that the frameshift signals of the SARS-associated coronavirus and mouse hepatitis virus have evolved to promote optimal frameshift efficiencies. Finally, we show that a previously described frameshift attenuator element does not actually affect frameshifting per se but rather serves to limit the fraction of ribosomes available for frameshifting. The findings of these analyses all support a \u201cgolden mean\u201d model in which viruses use both programmed ribosomal frameshifting and translational attenuation to control the relative ratios of their encoded proteins.<\/jats:p>","DOI":"10.1128\/jvi.02480-09","type":"journal-article","created":{"date-parts":[[2010,2,17]],"date-time":"2010-02-17T21:11:49Z","timestamp":1266441109000},"page":"4330-4340","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":139,"title":["Achieving a Golden Mean: Mechanisms by Which Coronaviruses Ensure Synthesis of the Correct Stoichiometric Ratios of Viral Proteins"],"prefix":"10.1128","volume":"84","author":[{"given":"Ewan P.","family":"Plant","sequence":"first","affiliation":[{"name":"Laboratory of Hepatitis and Related Emerging Agents, Division of Emerging and Transfusion-Transmitted Diseases, Office of Blood Research and Review, CBER, FDA, 8800 Rockville Pike, HFM310, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasa","family":"Rakauskaite\u0307","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, Microbiology Building, Room 2135, University of Maryland, College Park, Maryland 20742"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah R.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatitis and Related Emerging Agents, Division of Emerging and Transfusion-Transmitted Diseases, Office of Blood Research and Review, CBER, FDA, 8800 Rockville Pike, HFM310, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Dinman","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, Microbiology Building, Room 2135, University of Maryland, College Park, Maryland 20742"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00385-06"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.1.172"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162223099"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.4.2082-2087.2004"},{"key":"e_1_3_2_6_2","first-page":"1","volume":"287","year":"2005","unstructured":"Brian, D. A., and R. S. Baric. 2005. Coronavirus genome structure and replication. Curr. Top. Microbiol. Immunol.287:1-30.","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-76-8-1885"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90124-4"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(92)90901-U"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(91)90361-9"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.34.100180.000405"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.5.975"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1726"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.3.1506"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00956.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/522431"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.1.174"},{"key":"e_1_3_2_18_2","first-page":"870","volume":"3","year":"1997","unstructured":"Dinman, J. D., and T. G. Kinzy. 1997. Translational misreading: mutations in translation elongation factor 1alpha differentially affect programmed ribosomal frameshifting and drug sensitivity. RNA3:870-881.","journal-title":"RNA"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7799(97)01167-0"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.6.3669-3676.1992"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/141.1.95"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-006-0840-x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.6.5.1552-1561.1986"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.60.1.103-134.1996"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.6.2179-2182.1988"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2008.06.008"},{"key":"e_1_3_2_27_2","first-page":"479","volume":"4","year":"1998","unstructured":"Grentzmann, G., J. A. Ingram, P. J. Kelly, R. F. Gesteland, and J. F. Atkins. 1998. A dual-luciferase reporter system for studying recoding signals. RNA4:479-486.","journal-title":"RNA"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2001.0997"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2000.0647"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.6.4819-4824.1998"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(90)90336-P"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"e160","DOI":"10.1093\/nar\/gnh157","volume":"32","year":"2004","unstructured":"Jacobs, J. L., and J. D. Dinman. 2004. Systematic analysis of bicistronic reporter assay data. Nucleic Acids Res.32:e160.","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1993.1174"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/135.2.309"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.24.8657-8670.2001"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm404"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2700"},{"key":"e_1_3_2_38_2","first-page":"1641","volume":"84","year":"2009","unstructured":"Melian, E. B., E. Hinzman, T. Nagasaki, A. E. Firth, N. M. Wills, A. S. Nouwens, B. J. Blitvich, J. Leung, A. Funk, J. F. Atkins, R. Hall, and A. A. Khromykh. 2009. NS1\u2032 of flaviviruses in the Japanese encephalitis serogroup is a product of ribosomal frameshifting and plays a role in viral neuro-invasiveness. J. Virol.84:1641-1647.","journal-title":"J. Virol."},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.5.1602-1613.2003"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1355838201001480"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2165803"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003299"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.9.5111-5117.1991"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4801"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.1.384"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2225206"},{"key":"e_1_3_2_47_2","first-page":"4873","volume":"13","year":"2008","unstructured":"Plant, E. P., and J. D. Dinman. 2008. The role of programmed-1 ribosomal frameshifting in coronavirus propagation. Front. Biosci.13:4873-4881.","journal-title":"Front. Biosci."},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030172"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/16.4.334"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8721"},{"key":"e_1_3_2_51_2","first-page":"31","volume":"287","year":"2005","unstructured":"Sawicki, S. G., and D. L. Sawicki. 2005. Coronavirus transcription: a perspective. Curr. Top. Microbiol. Immunol.287:31-55.","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.11.6931-6940.1993"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki731"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.15.7868-7873.2002"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-007-0079-y"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.14.6676-6681.2001"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.19424-0"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.249"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1735582100"},{"key":"e_1_3_2_60_2","first-page":"57","volume":"287","year":"2005","unstructured":"Ziebuhr, J. 2005. The coronavirus replicase. Curr. Top. Microbiol. Immunol.287:57-94.","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg595"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02480-09","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02480-09","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T08:56:31Z","timestamp":1646470591000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.02480-09"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5]]},"references-count":60,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2010,5]]}},"alternative-id":["10.1128\/JVI.02480-09"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02480-09","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5]]},"assertion":[{"value":"2009-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-02-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}