{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:30:07Z","timestamp":1790501407183,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 -AI095753-01A1"],"award-info":[{"award-number":["R01 -AI095753-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,1]]},"DOI":"10.1093\/ve\/vey001","type":"journal-article","created":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T07:08:27Z","timestamp":1517900907000},"source":"Crossref","is-referenced-by-count":24,"title":["Mosquito bottlenecks alter viral mutant swarm in a tissue and time-dependent manner with contraction and expansion of variant positions and diversity"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-0848","authenticated-orcid":false,"given":"Edward I","family":"Patterson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Khanipov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M","family":"Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany F","family":"Kautz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dedeke","family":"Rockx-Brouwer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgiy","family":"Golovko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levent","family":"Albayrak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriy","family":"Fofanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi L","family":"Forrester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,2,15]]},"reference":[{"key":"key\n\t\t\t\t20180215082645_vey001-B1","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1126\/science.1115030","article-title":"Long-Term Transmission of Defective RNA Viruses in Humans and Aedes Mosquitoes","volume":"311","author":"Aaskov","year":"2006","journal-title":"Science (New York, N.Y.)"},{"key":"key\n\t\t\t\t20180215082645_vey001-B2","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nature12861","article-title":"Mutation and Fitness Landscapes of an RNA Virus Revealed through Population Sequencing","volume":"505","author":"Acevedo","year":"2014","journal-title":"Nature"},{"key":"key\n\t\t\t\t20180215082645_vey001-B3","doi-asserted-by":"crossref","DOI":"10.1103\/PhysRevLett.100.038106","article-title":"Effects of Spatial Competition on the Diversity of a Quasispecies\u2019","volume":"100","author":"Aguirre","year":"2008","journal-title":"Physical Review Letters"},{"key":"key\n\t\t\t\t20180215082645_vey001-B4","author":"Andrews","year":"2015"},{"key":"key\n\t\t\t\t20180215082645_vey001-B5","doi-asserted-by":"crossref","first-page":"4994","DOI":"10.1073\/pnas.0509961103","article-title":"Venezuelan Encephalitis Emergence Mediated by a Phylogenetically Predicted Viral Mutation\u2019","volume":"103","author":"Anishchenko","year":"2006","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"key\n\t\t\t\t20180215082645_vey001-B6","doi-asserted-by":"crossref","first-page":"e1004838","DOI":"10.1371\/journal.ppat.1004838","article-title":"Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype","volume":"11","author":"Borderia","year":"2015","journal-title":"PLoS Pathogens"},{"key":"key\n\t\t\t\t20180215082645_vey001-B7","doi-asserted-by":"crossref","first-page":"e1000502","DOI":"10.1371\/journal.ppat.1000502","article-title":"RNAi Targeting of West Nile Virus in Mosquito Midguts Promotes Virus Diversitification\u2019","volume":"5","author":"Brackney","year":"2009","journal-title":"PLoS Pathogens"},{"key":"key\n\t\t\t\t20180215082645_vey001-B8","doi-asserted-by":"crossref","first-page":"e24466","DOI":"10.1371\/journal.pone.0024466","article-title":"West Nile Virus Genetic Diversity Is Maintained during Transmission by Culex pipiens Quinquefasciatus Mosquitoes\u2019","volume":"6","author":"Brackney","year":"2011","journal-title":"PLoS One"},{"key":"key\n\t\t\t\t20180215082645_vey001-B9","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1128\/JVI.76.4.1718-1730.2002","article-title":"Positively Charged Amino Acid Substitutions in the E2 Envelope Glycoprotein Are Associated with the Emergence of Venezuelan Equine Encephalitis Virus\u2019","volume":"76","author":"Brault","year":"2002","journal-title":"Journal of Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B10","doi-asserted-by":"crossref","first-page":"11344","DOI":"10.1073\/pnas.0402905101","article-title":"Venezuelan Equine Encephalitis Emergence: Enhanced Vector Infection from a Single Amino Acid Substitution in the Envelope Glycoprotein\u2019","volume":"101","author":"Brault","year":"2004","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"key\n\t\t\t\t20180215082645_vey001-B11","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.coviro.2014.03.010","article-title":"The Long and Short of Antiviral Defense: Small RNA-Based Immunity in Insects\u2019","volume":"7","author":"Bronkhorst","year":"2014","journal-title":"Current Opinion in Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B12","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.meegid.2012.01.022","article-title":"Quantification of Intrahost Bottlenecks of West Nile Virus in Culex pipiens Mosquitoes Using an Artificial Mutant Swarm\u2019","volume":"12","author":"Ciota","year":"2012","journal-title":"Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases"},{"key":"key\n\t\t\t\t20180215082645_vey001-B13","doi-asserted-by":"crossref","first-page":"e7876","DOI":"10.1371\/journal.pone.0007876","article-title":"Experimental Passage of St. Louis Encephalitis Virus in Vivo in Mosquitoes and Chickens Reveals Evolutionarily Significant Virus Characteristics","volume":"17","author":"Ciota","year":"2009","journal-title":"PLoS One"},{"key":"key\n\t\t\t\t20180215082645_vey001-B14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.virol.2006.08.005","article-title":"Cell-Specific Adaptation of Two Flaviviruses following Serial Passage in Mosquito Cell Culture\u2019","volume":"357","author":"Ciota","year":"2007","journal-title":"Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B15","doi-asserted-by":"crossref","first-page":"16038","DOI":"10.1073\/pnas.1111650108","article-title":"Arbovirus High Fidelity Variant Loses Fitness in Mosquitoes and Mice\u2019","volume":"108","author":"Coffey","year":"2011","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"key\n\t\t\t\t20180215082645_vey001-B16","doi-asserted-by":"crossref","first-page":"6970","DOI":"10.1073\/pnas.0712130105","article-title":"Arbovirus Evolution in Vivo Is Constrained by Host Alternation","volume":"105","author":"Coffey","year":"2008","journal-title":"Proceedings of the National Academy of Sciencesof the United States of America"},{"key":"key\n\t\t\t\t20180215082645_vey001-B17","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.virusres.2004.11.003","article-title":"Quasispecies Dynamics and RNA Virus Extinction\u2019","volume":"107","author":"Domingo","year":"2005","journal-title":"Virus Research"},{"key":"key\n\t\t\t\t20180215082645_vey001-B18","doi-asserted-by":"crossref","first-page":"11555","DOI":"10.1128\/JVI.79.18.11555-11558.2005","article-title":"Adaptive Value of High Mutation Rates of RNA Viruses: Separating Causes from Consequences\u2019","volume":"79","author":"Elena","year":"2005","journal-title":"Journal of Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B19","first-page":"141","article-title":"Population Bottlenecks in Quasispecies Dynamics","volume":"299","author":"Escarmis","year":"2006","journal-title":"Quasispecies: Concept and Implications for Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B20","doi-asserted-by":"crossref","first-page":"8709","DOI":"10.1128\/JVI.00165-11","article-title":"Analysis of Intrahost Variation in Venezuelan Equine Encephalitis Virus Reveals Repeated Deletions in the 6-Kilodalton Protein Gene\u2019","volume":"85","author":"Forrester","year":"2011","journal-title":"Journal of Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B21","doi-asserted-by":"crossref","first-page":"e1002897","DOI":"10.1371\/journal.ppat.1002897","article-title":"Vector-Borne Transmissions Imposes a Severe Bottleneck on an RNA Virus Population\u2019","volume":"8","author":"Forrester","year":"2012","journal-title":"PLoS Pathogens"},{"key":"key\n\t\t\t\t20180215082645_vey001-B22","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.virusres.2007.07.001","article-title":"Characterization of Minority Subpopulations in the Mutant Spectrum of HIV-1 Quasispecies by Successive Specific Amplifications\u2019","volume":"129","author":"Garcia-Arriaza","year":"2007","journal-title":"Virus Research"},{"key":"key\n\t\t\t\t20180215082645_vey001-B23","doi-asserted-by":"crossref","first-page":"9128","DOI":"10.1128\/JVI.79.14.9128-9133.2005","article-title":"Envelope Glycoprotein Mutations Mediate Equine Amplificiation and Virulence of Epizootic Venezuelan Equine Encephalitis Virus\u2019","volume":"79","author":"Greene","year":"2005","journal-title":"Journal of Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B24","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.chom.2016.03.002","article-title":"Genetic Drift during Systemic Arbovirus Infection of Mosquito Vectors Leads to Decreased Relative Fitness during Host Switching","volume":"19","author":"Grubaugh","year":"2016","journal-title":"Cell Host and Microbe"},{"key":"key\n\t\t\t\t20180215082645_vey001-B25","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.celrep.2017.03.076","article-title":"Mosquitoes Transmit Unique West Nile Virus Populations during Each Feeding Episode\u2019","volume":"19","author":"Grubaugh","year":"2017","journal-title":"Cell Reports"},{"key":"key\n\t\t\t\t20180215082645_vey001-B26","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1128\/JVI.03265-14","article-title":"Demographics of Natural Oral Infection of Mosquitoes by Venezuelan Equine Encephalitis Virus\u2019","volume":"89","author":"Gutierrez","year":"2015","journal-title":"Journal of Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B27","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1099\/vir.0.81015-0","article-title":"Genetic Variation in West Nile Virus from Naturally Infected Mosquitoes and Birds Suggests Quasispecies Structure and Strong Purifying Selection\u2019","volume":"86","author":"Jerzak","year":"2005","journal-title":"Journal of General Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B28","doi-asserted-by":"crossref","first-page":"e1001005","DOI":"10.1371\/journal.ppat.1001005","article-title":"Quasispecies Theory and the Behavior of RNA Viruses\u2019","volume":"6","author":"Lauring","year":"2010","journal-title":"PLoS Pathogens"},{"key":"key\n\t\t\t\t20180215082645_vey001-B29","doi-asserted-by":"crossref","first-page":"e1006111","DOI":"10.1371\/journal.pgen.1006111","article-title":"Genetic Drift, Purifying Selection and Vector Genotype Shape Dengue Virus Intra-Host Genetic Diversity in Mosquitoes\u2019","volume":"12","author":"Lequime","year":"2016","journal-title":"PLoS Genetics"},{"key":"key\n\t\t\t\t20180215082645_vey001-B30","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000339985","article-title":"Chikungunya Virus Induces a More Moderate Cytopathic Effect in Mosquito Cells than in Mammalian Cells\u2019","volume":"56","author":"Li","year":"2013","journal-title":"Intervirology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B31","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1109\/18.61115","article-title":"Divergence Measures Based on the Shannon Entropy\u2019","volume":"37","author":"Lin","year":"1991","journal-title":"IEEE Transactions on Information Theory"},{"key":"key\n\t\t\t\t20180215082645_vey001-B32","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1098\/rstb.2010.0076","article-title":"Pathways to Extinction: Beyond the Error Threshold', Philosophicals","volume":"365","author":"Manrubia","year":"2010","journal-title":"Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences"},{"key":"key\n\t\t\t\t20180215082645_vey001-B33","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.gene.2004.12.033","article-title":"High Mutation Rates, Bottlenecks, and Robustness of Viral RNA Quasispecies\u2019","volume":"347","author":"Manrubia","year":"2005","journal-title":"Gene"},{"key":"key\n\t\t\t\t20180215082645_vey001-B34","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1086\/595703","article-title":"Minority Quasispecies of Drug-Resistant HIV-1 That Lead to Early Therapy Failure in Treatment-Naive and -Adherent Patients\u2019","volume":"48","author":"Metzner","year":"2009","journal-title":"Clinical Infectious Diseases"},{"key":"key\n\t\t\t\t20180215082645_vey001-B35","doi-asserted-by":"crossref","first-page":"387","DOI":"10.4161\/rna.6.4.8946","article-title":"Origins of alphavirus-Derived Small RNA's in Mosquitoes\u2019","volume":"6","author":"Myles","year":"2009","journal-title":"RNA Biology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B36","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1006\/viro.1996.0254","article-title":"Complete Sequence of Venezuelan Equine Encephalitis Virus Subtype IE Reveals Conserved and Hypervariable Domains within the C Terminus of nsP3\u2019","volume":"219","author":"Oberste","year":"1996","journal-title":"Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B37","doi-asserted-by":"crossref","first-page":"8546","DOI":"10.1128\/JVI.00736-12","article-title":"Genome-Wide Patterns of Intrahuman Dengue Virus Diversity Reveal Associations with Viral Phylogenetic Clade and Intrahost Diversity\u2019","volume":"86","author":"Parameswaran","year":"2012","journal-title":"Journal of Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B38","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1042\/BST20140068","article-title":"Endogenous siRNAs, Regulators of Internal Affairs\u2019","volume":"42","author":"Piatek","year":"2014","journal-title":"Biochemical Society Transactions"},{"key":"key\n\t\t\t\t20180215082645_vey001-B39","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1093\/molbev\/msp289","article-title":"Phylogenetic Analysis of Population-Based and Deep Sequencing Data to Identify Coevolving Sites in the Nef Gene of HIV-1","volume":"27","author":"Poon","year":"2010","journal-title":"Molecular Biology and Evolution"},{"key":"key\n\t\t\t\t20180215082645_vey001-B40","doi-asserted-by":"crossref","first-page":"e1003877","DOI":"10.1371\/journal.ppat.1003877","article-title":"\u2018Alphavirus Mutator Variants Present Host-Specific Defects and Attenuation in Mammalian and Insect Models\u2019","volume":"10","author":"Rozen-Gagnon","year":"2014","journal-title":"PLoS Pathogens"},{"key":"key\n\t\t\t\t20180215082645_vey001-B41","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.1128\/JVI.74.8.3543-3547.2000","article-title":"Memory in Viral Quasispecies\u2019","volume":"74","author":"Ruiz-Jarabo","year":"2000","journal-title":"Journal of Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B42","doi-asserted-by":"crossref","first-page":"703","DOI":"10.4269\/ajtmh.1970.19.703","article-title":"Discovery and Geographic Distribution of Venezuelan Encephatlitis Virus in Guatemala, Honduras, and British Honduras during 1965-68, and Its Possible Movement to Central America and Mexico\u2019","volume":"19","author":"Scherer","year":"1970","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"key\n\t\t\t\t20180215082645_vey001-B43","doi-asserted-by":"crossref","first-page":"e0004052","DOI":"10.1371\/journal.pntd.0004052","article-title":"Tracking Dengue Virus Intra-Host Genetic Diversity during Human-to-Mosquito Transmission\u2019","volume":"9","author":"Sim","year":"2015","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"key\n\t\t\t\t20180215082645_vey001-B44","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.virol.2007.10.011","article-title":"Venezuelan Equine Encephalitis Virus in the Mosquito Vector Aedes Taeniorhynchus: Infection Initiated by a Small Number of Susceptible Epithelial Cells and a Population Bottleneck","volume":"372","author":"Smith","year":"2008","journal-title":"Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B45","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.3201\/eid1708.050841","article-title":"Venezuelan Equine Encephalitis Virus Transmission and Effect on Pathogenesis\u2019","volume":"12","author":"Smith","year":"2006","journal-title":"Emerging Infectious Diseases"},{"key":"key\n\t\t\t\t20180215082645_vey001-B46","doi-asserted-by":"crossref","first-page":"e0004402","DOI":"10.1371\/journal.pntd.0004402","article-title":"Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements\u2019","volume":"10","author":"Stapleford","year":"2016","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"key\n\t\t\t\t20180215082645_vey001-B47","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.chom.2014.05.008","article-title":"Emergence and Transmission of Arbovirus Evolutionary Intermediates with Epidemic Potential","volume":"15","author":"Stapleford","year":"2014","journal-title":"Cell Host and Microbe"},{"key":"key\n\t\t\t\t20180215082645_vey001-B48","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.virol.2012.01.036","article-title":"Point Mutations in the West Nile Virus (Flaviviridae; Flavivirus) RNA-Dependent RNA Polymerase Alter Viral Fitness in a Host-Dependent Manner in Vitro and in Vivo\u2019","volume":"427","author":"Van Slyke","year":"2012","journal-title":"Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B49","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nature04388","article-title":"Quasispecies Diversity Determines Pathogenesis through Co-Operative Interactions in a Viral Population\u2019","volume":"439","author":"Vignuzzi","year":"2006","journal-title":"Nature"},{"key":"key\n\t\t\t\t20180215082645_vey001-B50","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1097\/QAD.0b013e328329f964","article-title":"Increased Mutations in Env and Pol Suggest Greater HIV-1 Replication in Sputum-Compared to Blood-Derived Viruses\u2019","volume":"23","author":"Wagner","year":"2009","journal-title":"Aids"},{"key":"key\n\t\t\t\t20180215082645_vey001-B51","doi-asserted-by":"crossref","first-page":"6218","DOI":"10.1128\/JVI.02271-09","article-title":"HCV Transmission Bottlenecks Analyzed by Deep Sequencing","volume":"84","author":"Wang","year":"2010","journal-title":"Journal of Virology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B52","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev.ento.49.061802.123422","article-title":"Venezuelan Equine Encephalitis\u2019","volume":"49","author":"Weaver","year":"2004","journal-title":"Annual Review of Entomology"},{"key":"key\n\t\t\t\t20180215082645_vey001-B53","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1093\/oxfordjournals.molbev.a004059","article-title":"Reduced Positive Selection in Vector-Borne RNA Viruses\u2019","volume":"19","author":"Woelk","year":"2002","journal-title":"Molecular Biology and Evolution"}],"container-title":["Virus Evolution"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ve\/article-pdf\/4\/1\/vey001\/23956890\/vey001.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,2,15]],"date-time":"2018-02-15T08:27:03Z","timestamp":1518683223000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ve\/article\/doi\/10.1093\/ve\/vey001\/4862516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,1]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,2,15]]},"published-print":{"date-parts":[[2018,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ve\/vey001","relation":{},"ISSN":["2057-1577"],"issn-type":[{"value":"2057-1577","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,1]]},"published":{"date-parts":[[2018,1,1]]}}}