{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T07:11:41Z","timestamp":1769152301286,"version":"3.49.0"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T00:00:00Z","timestamp":1617580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Since their first sequencing 40 years ago, Dengue virus (DENV) genotypes have shown extreme coherence regarding the serotype class they encode. Considering that DENV is a ribonucleic acid (RNA) virus with a high mutation rate, this behavior is intriguing. Here, we explore the effect of various parameters on likelihood of new serotype emergence. In order to determine the time scales of such an event, we used a Timed Markov Transmission Model to explore the influences of sylvatic versus peri-urban transmission, viral mutation rate, and vertical transmission on the probabilities of novel serotype emergence. We found that around 1 000 years are required for a new serotype to emerge, consistent with phylogenetic analysis of extant dengue serotypes. Furthermore, we show that likelihood of establishing chains of mosquito-human-mosquito infection, known as consolidation, is the primary factor which constrains novel serotype emergence. Our work illustrates the restrictions on and provides a mechanistic explanation for the low probability of novel dengue virus serotype emergence and the low number of observed DENV serotypes.<\/jats:p>","DOI":"10.1371\/journal.pone.0248765","type":"journal-article","created":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T17:36:33Z","timestamp":1617644193000},"page":"e0248765","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Probability of consolidation constrains novel serotype emergence in dengue fever virus"],"prefix":"10.1371","volume":"16","author":[{"given":"Gilberto","family":"S\u00e1nchez-Gonz\u00e1lez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachery R.","family":"Belak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Lozano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9928-8937","authenticated-orcid":true,"given":"Renaud","family":"Cond\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,4,5]]},"reference":[{"key":"pone.0248765.ref001","article-title":"The growing burden of dengue in Latin America","author":"R Tapia-Conyer","year":"2009","journal-title":"J Clin Virol"},{"key":"pone.0248765.ref002","article-title":"Efficacy of a tetravalent dengue vaccine in children in Latin America","author":"RF Hamdy","year":"2015","journal-title":"Journal of the Pediatric Infectious Diseases Society"},{"key":"pone.0248765.ref003","article-title":"Immunodominance Changes as a Function of the Infecting Dengue Virus Serotype and Primary versus Secondary Infection","author":"D Weiskopf","year":"2014","journal-title":"J Virol"},{"key":"pone.0248765.ref004","article-title":"A systematic review of the prevalence of mucosal and cutaneous human papillomavirus types","author":"D Bzhalava","year":"2013","journal-title":"Virology"},{"key":"pone.0248765.ref005","article-title":"Isolation of monoclonal antibodies\u2014Escape variant of dengue virus serotype I","author":"SK Chua","year":"2006","journal-title":"Singapore Med J"},{"key":"pone.0248765.ref006","article-title":"Residues in domain III of the dengue virus envelope glycoprotein involved in cell-surface glycosaminoglycan binding","author":"D Watterson","year":"2012","journal-title":"J Gen Virol"},{"key":"pone.0248765.ref007","article-title":"Antibodies to Envelope Glycoprotein of Dengue Virus during the Natural Course of Infection Are Predominantly Cross-Reactive and Recognize Epitopes Containing Highly Conserved Residues at the Fusion Loop of Domain II","author":"C-Y Lai","year":"2008","journal-title":"J Virol"},{"key":"pone.0248765.ref008","article-title":"Variable Surface Epitopes in the Crystal Structure of Dengue Virus Type 3 Envelope Glycoprotein","author":"Y Modis","year":"2005","journal-title":"J Virol"},{"key":"pone.0248765.ref009","article-title":"A ligand-binding pocket in the dengue virus envelope glycoprotein","author":"Y Modis","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0248765.ref010","article-title":"Natural strain variation and antibody neutralization of dengue serotype 3 viruses","author":"WMPB Wahala","year":"2010","journal-title":"PLoS Pathog"},{"key":"pone.0248765.ref011","article-title":"The origin, emergence and evolutionary genetics of dengue virus","author":"EC Holmes","year":"2003","journal-title":"Infection, Genetics and Evolution"},{"key":"pone.0248765.ref012","article-title":"Ecology of dengue virus","author":"A. 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