{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:22:38Z","timestamp":1791822158548,"version":"4.3.4"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T00:00:00Z","timestamp":1482105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T00:00:00Z","timestamp":1482105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since their commercialization, vaccines against <jats:italic>Porcine circovirus type 2<\/jats:italic> (PCV2) have been the cornerstone control strategy. Nevertheless, the periodic emergence of new genotype waves and the recent reports of vaccine failure outbreaks have raised the question if widespread vaccination strategies could have driven viral evolution and affected different genotype fitness. To investigate this issue an in-deep analysis, based on a bioinformatics and biostatistics approach, has been implemented. ORF2 sequences from vaccinated and non-vaccinated populations (i.e. domestic pigs before and after vaccine introduction and wild boars) were considered. The action of selective forces on PCV2 strains has been analyzed and compared among groups. Remarkable differences were found in the selective forces acting on viral populations circulating in different \u201cimmune environments\u201d. Particularly for PCV2a, a directional selection promoting a change in the viral capsid away from the vaccine specific antigenic determinants has been detected after vaccine introduction. Involved amino acids were previously reported to be part of viral epitopes whose variability is responsible of immune escape. Our findings support a change in PCV2 evolutionary pattern after widespread vaccination introduction and stress once more the compulsoriness of a continuous monitoring of PCV2 epidemiology to promptly act in response to the emergence of possible vaccine-escaping mutants.<\/jats:p>","DOI":"10.1038\/srep39458","type":"journal-article","created":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T10:15:26Z","timestamp":1482142526000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Porcine circovirus type 2 (PCV2) evolution before and after the vaccination introduction: A large scale epidemiological study"],"prefix":"10.1038","volume":"6","author":[{"given":"Giovanni","family":"Franzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Maria","family":"Tucciarone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Cecchinato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Drigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,19]]},"reference":[{"key":"BFsrep39458_CR1","doi-asserted-by":"publisher","first-page":"612","DOI":"10.7589\/0090-3558-48.3.612","volume":"48","author":"M Fabisiak","year":"2012","unstructured":"Fabisiak, M., Szczotka, A., Podg\u00f3rska, K. & Stadejek, T. Prevalence of infection and genetic diversity of porcine circovirus type 2 (PCV2) in wild boar (Sus scrofa) in Poland. J. Wildl. Dis. 48, 612\u2013618 (2012).","journal-title":"J. Wildl. Dis."},{"key":"BFsrep39458_CR2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.vetmic.2012.12.033","volume":"165","author":"J Segal\u00e9s","year":"2013","unstructured":"Segal\u00e9s, J. et al. The natural history of porcine circovirus type 2: from an inoffensive virus to a devastating swine disease? Vet. Microbiol. 165, 13\u201320 (2013).","journal-title":"Vet. Microbiol."},{"key":"BFsrep39458_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11262-014-1099-z","volume":"49","author":"QZ Lv","year":"2014","unstructured":"Lv, Q. Z., Guo, K. K. & Zhang, Y. M. Current understanding of genomic DNA of porcine circovirus type 2. Virus Genes 49, 1\u201310 (2014).","journal-title":"Virus Genes"},{"key":"BFsrep39458_CR4","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1079\/AHR2005106","volume":"6","author":"J Segales","year":"2005","unstructured":"Segales, J., Allan, G. M. & Domingo, M. Porcine circovirus diseases. Anim. Health Res. Rev. 6, 119\u2013142 (2005).","journal-title":"Anim. Health Res. Rev."},{"key":"BFsrep39458_CR5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.virusres.2011.10.007","volume":"164","author":"J Segal\u00e9s","year":"2012","unstructured":"Segal\u00e9s, J. & Segales, J. Porcine circovirus type 2 (PCV2) infections: Clinical signs, pathology and laboratory diagnosis. Virus Res. 164, 10\u201319 (2012).","journal-title":"Virus Res."},{"key":"BFsrep39458_CR6","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.virusres.2011.09.041","volume":"164","author":"NM Beach","year":"2012","unstructured":"Beach, N. M. & Meng, X.-J. Efficacy and future prospects of commercially available and experimental vaccines against porcine circovirus type 2 (PCV2). Virus Res. 164, 33\u201342 (2012).","journal-title":"Virus Res."},{"key":"BFsrep39458_CR7","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.virusres.2011.12.002","volume":"164","author":"N Rose","year":"2012","unstructured":"Rose, N., Opriessnig, T., Grasland, B. & Jestin, A. Epidemiology and transmission of porcine circovirus type 2 (PCV2). Virus Res. 164, 78 (2012).","journal-title":"Virus Res."},{"key":"BFsrep39458_CR8","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1007\/s11262-013-0933-z","volume":"47","author":"Z Gao","year":"2013","unstructured":"Gao, Z. et al. Identification and characterization of two novel transcription units of porcine circovirus 2. Virus Genes 47, 268\u2013275 (2013).","journal-title":"Virus Genes"},{"key":"BFsrep39458_CR9","doi-asserted-by":"publisher","first-page":"e0127859","DOI":"10.1371\/journal.pone.0127859","volume":"10","author":"Q Lv","year":"2015","unstructured":"Lv, Q., Guo, K., Xu, H., Wang, T. & Zhang, Y. Identification of Putative ORF5 Protein of Porcine Circovirus Type 2 and Functional Analysis of GFP-Fused ORF5 Protein. PLoS One 10, e0127859 (2015).","journal-title":"PLoS One"},{"key":"BFsrep39458_CR10","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.virusres.2011.10.012","volume":"164","author":"AK Cheung","year":"2012","unstructured":"Cheung, A. K. Porcine circovirus: Transcription and DNA replication. Virus Res. 164, 46 (2012).","journal-title":"Virus Res."},{"key":"BFsrep39458_CR11","doi-asserted-by":"publisher","first-page":"7856","DOI":"10.1128\/JVI.00737-11","volume":"85","author":"R Khayat","year":"2011","unstructured":"Khayat, R. et al. The 2.3-angstrom structure of porcine circovirus 2. J. Virol. 85, 7856\u20137862 (2011).","journal-title":"J. Virol."},{"key":"BFsrep39458_CR12","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1099\/0022-1317-81-9-2281","volume":"81","author":"P Nawagitgul","year":"2000","unstructured":"Nawagitgul, P. et al. Open reading frame 2 of porcine circovirus type 2 encodes a major capsid protein. J. Gen. Virol. 81, 2281 (2000).","journal-title":"J. Gen. Virol."},{"key":"BFsrep39458_CR13","doi-asserted-by":"crossref","unstructured":"Franzo, G., Cortey, M., Segal\u00e9s, J., Hughes, J. & Drigo, M. Phylodynamic analysis of porcine circovirus type 2 reveals global waves of emerging genotypes and the circulation of recombinant forms. Mol. Phylogenet. Evol. 100 (2016).","DOI":"10.1016\/j.ympev.2016.04.028"},{"key":"BFsrep39458_CR14","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.virusres.2011.10.019","volume":"163","author":"PMP Vidigal","year":"2012","unstructured":"Vidigal, P. M. P. et al. Tripping over emerging pathogens around the world: a phylogeographical approach for determining the epidemiology of Porcine circovirus-2 (PCV-2), considering global trading. Virus Res. 163, 320\u2013327 (2012).","journal-title":"Virus Res."},{"key":"BFsrep39458_CR15","doi-asserted-by":"crossref","unstructured":"Franzo, G. et al. Revisiting the taxonomical classification of Porcine Circovirus type 2 (PCV2): Still a real challenge. Virol. J. 12, (2015).","DOI":"10.1186\/s12985-015-0361-x"},{"key":"BFsrep39458_CR16","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.virol.2006.07.047","volume":"357","author":"A Olvera","year":"2007","unstructured":"Olvera, A., Cortey, M., Segal\u00e9s, J. & Segales, J. Molecular evolution of porcine circovirus type 2 genomes: phylogeny and clonality. Virology 357, 175\u2013185 (2007).","journal-title":"Virology"},{"key":"BFsrep39458_CR17","first-page":"259","volume":"72","author":"S Carman","year":"2008","unstructured":"Carman, S. et al. The emergence of a new strain of porcine circovirus-2 in Ontario and Quebec swine and its association with severe porcine circovirus associated disease\u20132004\u20132006. Can. J. Vet. Res. 72, 259\u2013268 (2008).","journal-title":"Can. J. Vet. Res."},{"key":"BFsrep39458_CR18","first-page":"1","volume":"9","author":"M Constans","year":"2015","unstructured":"Constans, M., Ssemadaali, M., Kolyvushko, O. & Ramamoorthy, S. Antigenic Determinants of Possible Vaccine Escape by Porcine Circovirus Subtype 2b Viruses. Bioinform. Biol. Insights 9, 1 (2015).","journal-title":"Bioinform. Biol. Insights"},{"key":"BFsrep39458_CR19","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1186\/1743-422X-7-273","volume":"7","author":"LJ Guo","year":"2010","unstructured":"Guo, L. J., Lu, Y. H., Wei, Y. W., Huang, L. P. & Liu, C. M. Porcine circovirus type 2 (PCV2): genetic variation and newly emerging genotypes in China. Virol. J. 7, 273 (2010).","journal-title":"Virol. J."},{"key":"BFsrep39458_CR20","doi-asserted-by":"crossref","unstructured":"Xiao, C. T., Halbur, P. G. & Opriessnig, T. Global molecular genetic analysis of porcine circovirus type 2 (PCV2) sequences confirms the presence of four main PCV2 genotypes and reveals a rapid increase of PCV2d. J. Gen. Virol., doi: vir.0.000100 [pii] (2015).","DOI":"10.1099\/vir.0.000100"},{"key":"BFsrep39458_CR21","doi-asserted-by":"publisher","first-page":"12813","DOI":"10.1128\/JVI.01719-09","volume":"83","author":"C Firth","year":"2009","unstructured":"Firth, C., Charleston, M. A., Duffy, S., Shapiro, B. & Holmes, E. C. Insights into the evolutionary history of an emerging livestock pathogen: porcine circovirus 2. J. Virol. 83, 12813\u201312821 (2009).","journal-title":"J. Virol."},{"key":"BFsrep39458_CR22","doi-asserted-by":"crossref","unstructured":"Shen, H. G., Halbur, P. G. & Opriessnig, T. Prevalence and phylogenetic analysis of the current porcine circovirus 2 genotypes after implementation of widespread vaccination programmes in the USA. J. Gen. Virol., doi: 10.1099\/vir.0.039552-0 (2012).","DOI":"10.1099\/vir.0.039552-0"},{"key":"BFsrep39458_CR23","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.tvjl.2012.06.031","volume":"194","author":"C Chae","year":"2012","unstructured":"Chae, C. Commercial porcine circovirus type 2 vaccines: Efficacy and clinical application. Vet. J. 194, 151 (2012).","journal-title":"Vet. J."},{"key":"BFsrep39458_CR24","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1586\/14760584.2015.983084","volume":"14","author":"J Segal\u00e9s","year":"2015","unstructured":"Segal\u00e9s, J. Best practice and future challenges for vaccination against porcine circovirus type 2. Expert Rev. Vaccines 14, 473\u2013487 (2015).","journal-title":"Expert Rev. Vaccines"},{"key":"BFsrep39458_CR25","doi-asserted-by":"publisher","first-page":"3107","DOI":"10.1007\/s00705-014-2164-6","volume":"159","author":"HW Seo","year":"2014","unstructured":"Seo, H. W. et al. Genetic and antigenic characterization of a newly emerging porcine circovirus type 2b mutant first isolated in cases of vaccine failure in Korea. Arch. Virol. 159, 3107\u20133111 (2014).","journal-title":"Arch. Virol."},{"key":"BFsrep39458_CR26","first-page":"12412","volume":"86","author":"C-TT Xiao","year":"2012","unstructured":"Xiao, C.-T. T., Halbur, P. G. & Opriessnig, T. Complete genome sequence of a novel porcine circovirus type 2b variant present in cases of vaccine failures in the United States. J. Virol. 86, 12412\u201312469 (2012).","journal-title":"J. Virol."},{"key":"BFsrep39458_CR27","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.vaccine.2013.11.010","volume":"32","author":"T Opriessnig","year":"2014","unstructured":"Opriessnig, T., Gerber, P. F., Xiao, C.-T., Mogler, M. & Halbur, P. G. A commercial vaccine based on PCV2a and an experimental vaccine based on a variant mPCV2b are both effective in protecting pigs against challenge with a 2013 US variant mPCV2b strain. Vaccine 32, 230\u2013237 (2014).","journal-title":"Vaccine"},{"key":"BFsrep39458_CR28","doi-asserted-by":"publisher","first-page":"4342","DOI":"10.1016\/j.vaccine.2014.06.004","volume":"32","author":"T Opriessnig","year":"2014","unstructured":"Opriessnig, T. et al. Commercial PCV2a-based vaccines are effective in protecting naturally PCV2b-infected finisher pigs against experimental challenge with a 2012 mutant PCV2. Vaccine 32, 4342\u20134348 (2014).","journal-title":"Vaccine"},{"key":"BFsrep39458_CR29","doi-asserted-by":"publisher","first-page":"4158","DOI":"10.1016\/j.vaccine.2005.03.017","volume":"23","author":"D FitzSimons","year":"2005","unstructured":"FitzSimons, D. et al. Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants. Vaccine 23, 4158\u20134166 (2005).","journal-title":"Vaccine"},{"key":"BFsrep39458_CR30","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.vetmic.2010.04.014","volume":"146","author":"M Cecchinato","year":"2010","unstructured":"Cecchinato, M. et al. Avian metapneumovirus (AMPV) attachment protein involvement in probable virus evolution concurrent with mass live vaccine introduction. Vet. Microbiol. 146, 24\u201334 (2010).","journal-title":"Vet. Microbiol."},{"key":"BFsrep39458_CR31","first-page":"139","volume":"2","author":"AF Read","year":"2008","unstructured":"Read, A. F. & Mackinnon, M. J. Pathogen evolution in a vaccinated world. Evol. Heal. Dis. 2, 139\u2013152 (2008).","journal-title":"Evol. Heal. Dis"},{"key":"BFsrep39458_CR32","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.rvsc.2015.10.006","volume":"103","author":"MA Ssemadaali","year":"2015","unstructured":"Ssemadaali, M. A., Ilha, M. & Ramamoorthy, S. Genetic diversity of porcine circovirus type 2 and implications for detection and control. Res. Vet. Sci. 103, 179\u2013186 (2015).","journal-title":"Res. Vet. Sci."},{"key":"BFsrep39458_CR33","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1099\/vir.0.065318-0","volume":"95","author":"T Kekarainen","year":"2014","unstructured":"Kekarainen, T., Gonzalez, A., Llorens, A. & Segal\u00e9s, J. Genetic variability of porcine circovirus 2 in vaccinating and non-vaccinating commercial farms. J. Gen. Virol. 95, 1734\u20131742 (2014).","journal-title":"J. Gen. Virol."},{"key":"BFsrep39458_CR34","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.meegid.2015.04.004","volume":"32","author":"Giovanni Franzo","year":"2015","unstructured":"Franzo, G. et al. International trades, local spread and viral evolution: The case of porcine circovirus type 2 (PCV2) strains heterogeneity in Italy. Infect. Genet. Evol. 32 (2015).","journal-title":"Infection, Genetics and Evolution"},{"key":"BFsrep39458_CR35","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.tvjl.2007.02.017","volume":"176","author":"F Ruiz-Fons","year":"2008","unstructured":"Ruiz-Fons, F., Segales, J. & Gortazar, C. A review of viral diseases of the European wild boar: effects of population dynamics and reservoir role. Vet. J. 176, 158\u2013169 (2008).","journal-title":"Vet. J."},{"key":"BFsrep39458_CR36","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1051\/vetres:2004008","volume":"35","author":"J Vicente","year":"2004","unstructured":"Vicente, J. et al. Epidemiological study on porcine circovirus type 2 (PCV2) infection in the European wild boar (Sus scrofa). Vet. Res. 35, 243\u2013253 (2004).","journal-title":"Vet. Res."},{"key":"BFsrep39458_CR37","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1556\/avet.2012.035","volume":"60","author":"I Toplak","year":"2012","unstructured":"Toplak, I. et al. Study of the genetic variability of porcine circovirus type 2 detected in Serbia and Slovenia. Acta Vet. Hung. 60, 409\u2013420 (2012).","journal-title":"Acta Vet. Hung."},{"key":"BFsrep39458_CR38","doi-asserted-by":"publisher","first-page":"e103","DOI":"10.1016\/j.rvsc.2011.03.002","volume":"91","author":"MA Turcitu","year":"2011","unstructured":"Turcitu, M. A. et al. Genetic diversity of porcine circovirus type 2 (PCV2) in the Romanian wild boar population. Res. Vet. Sci. 91, e103\u2013e106 (2011).","journal-title":"Res. Vet. Sci."},{"key":"BFsrep39458_CR39","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.pt.2009.11.009","volume":"26","author":"PD Williams","year":"2010","unstructured":"Williams, P. D. Darwinian interventions: taming pathogens through evolutionary ecology. Trends Parasitol. 26, 83\u201392 (2010).","journal-title":"Trends Parasitol."},{"key":"BFsrep39458_CR40","doi-asserted-by":"publisher","first-page":"e1002198","DOI":"10.1371\/journal.pbio.1002198","volume":"13","author":"AF Read","year":"2015","unstructured":"Read, A. F. et al. Imperfect vaccination can enhance the transmission of highly virulent pathogens. PLoS Biol 13, e1002198 (2015).","journal-title":"PLoS Biol"},{"key":"BFsrep39458_CR41","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.vetmic.2012.12.019","volume":"163","author":"T Opriessnig","year":"2013","unstructured":"Opriessnig, T., Xiao, C.-T. T., Gerber, P. F. & Halbur, P. G. Emergence of a novel mutant PCV2b variant associated with clinical PCVAD in two vaccinated pig farms in the US concurrently infected with PPV2. Vet. Microbiol. 163, 177\u2013183 (2013).","journal-title":"Vet. Microbiol."},{"key":"BFsrep39458_CR42","doi-asserted-by":"publisher","first-page":"e41463","DOI":"10.1371\/journal.pone.0041463","volume":"7","author":"L Guo","year":"2012","unstructured":"Guo, L. et al. A porcine circovirus type 2 (PCV2) mutant with 234 amino acids in capsid protein showed more virulence in vivo, compared with classical PCV2a\/b strain. PLoS One 7, e41463 (2012).","journal-title":"PLoS One"},{"key":"BFsrep39458_CR43","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.vetmic.2015.07.026","volume":"180","author":"G Reiner","year":"2015","unstructured":"Reiner, G., Hofmeister, R. & Willems, H. Genetic variability of porcine circovirus 2 (PCV2) field isolates from vaccinated and non-vaccinated pig herds in Germany. Vet. Microbiol. 180, 41\u201348 (2015).","journal-title":"Vet. Microbiol."},{"key":"BFsrep39458_CR44","first-page":"1815","volume":"81","author":"D Mahe","year":"2000","unstructured":"Mahe, D. et al. Differential recognition of ORF2 protein from type 1 and type 2 porcine circoviruses and identification of immunorelevant epitopes. J. Gen. Virol. 81, 1815\u20131824 (2000).","journal-title":"J. Gen. Virol"},{"key":"BFsrep39458_CR45","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.molimm.2008.10.028","volume":"46","author":"S-B Shang","year":"2009","unstructured":"Shang, S.-B. et al. Fine mapping of antigenic epitopes on capsid proteins of porcine circovirus, and antigenic phenotype of porcine circovirus type 2. Mol. Immunol. 46, 327\u2013334 (2009).","journal-title":"Mol. Immunol."},{"key":"BFsrep39458_CR46","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1128\/CVI.00418-10","volume":"18","author":"BR Trible","year":"2011","unstructured":"Trible, B. R. et al. Antibody recognition of porcine circovirus type 2 capsid protein epitopes after vaccination, infection, and disease. Clin. Vaccine Immunol. 18, 749\u2013757 (2011).","journal-title":"Clin. Vaccine Immunol."},{"key":"BFsrep39458_CR47","doi-asserted-by":"publisher","first-page":"8135","DOI":"10.1128\/JVI.78.15.8135-8145.2004","volume":"78","author":"P Lekcharoensuk","year":"2004","unstructured":"Lekcharoensuk, P. et al. Epitope mapping of the major capsid protein of type 2 porcine circovirus (PCV2) by using chimeric PCV1 and PCV2. J. Virol. 78, 8135\u20138145 (2004).","journal-title":"J. Virol."},{"key":"BFsrep39458_CR48","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.vetmic.2011.11.030","volume":"157","author":"D Saha","year":"2012","unstructured":"Saha, D. et al. Antigenic subtyping and epitopes\u2019 competition analysis of porcine circovirus type 2 using monoclonal antibodies. Vet. Microbiol. 157, 13\u201322 (2012).","journal-title":"Vet. Microbiol."},{"key":"BFsrep39458_CR49","doi-asserted-by":"crossref","unstructured":"Martin, D. P., Murrell, B., Golden, M., Khoosal, A. & Muhire, B. RDP4: Detection and analysis of recombination patterns in virus genomes. Virus Evol. 1(1), doi: 10.1093\/ve\/vev003 (2015).","DOI":"10.1093\/ve\/vev003"},{"key":"BFsrep39458_CR50","first-page":"7","volume":"24","author":"D Burch","year":"2008","unstructured":"Burch, D. Porcine circovirus vaccines \u2013 where are we? Pig Prog. 24, 7\u20139 (2008).","journal-title":"Pig Prog."},{"key":"BFsrep39458_CR51","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1093\/molbev\/mst010","volume":"30","author":"K Katoh","year":"2013","unstructured":"Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30, 772\u2013780 (2013).","journal-title":"Mol. Biol. Evol."},{"key":"BFsrep39458_CR52","doi-asserted-by":"publisher","first-page":"W7","DOI":"10.1093\/nar\/gkq291","volume":"38","author":"F Abascal","year":"2010","unstructured":"Abascal, F., Zardoya, R. & Telford, M. J. TranslatorX: Multiple alignment of nucleotide sequences guided by amino acid translations. Nucleic Acids Res. 38, W7\u2013W13 (2010).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep39458_CR53","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1093\/molbev\/mss075","volume":"29","author":"AJ Drummond","year":"2012","unstructured":"Drummond, A. J., Suchard, M. A., Xie, D. & Rambaut, A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol. Biol. Evol. 29, 1969 (2012).","journal-title":"Mol. Biol. Evol."},{"key":"BFsrep39458_CR54","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1038\/nmeth.2109","volume":"9","author":"D Darriba","year":"2012","unstructured":"Darriba, D., Taboada, G. L., Doallo, R. & Posada, D. JModel Test 2: More models, new heuristics and parallel computing. Nat. Methods 9, 772 (2012).","journal-title":"Nat. Methods"},{"key":"BFsrep39458_CR55","doi-asserted-by":"crossref","unstructured":"Baele, G. F. A. U. et al. Improving the accuracy of demographic and molecular clock model comparison while accommodating phylogenetic uncertainty. Molecular biology and evolution JID 8501455, doi: 10.1093\/molbev\/mss084 (2012).","DOI":"10.1093\/molbev\/mss084"},{"key":"BFsrep39458_CR56","doi-asserted-by":"publisher","first-page":"e1002764","DOI":"10.1371\/journal.pgen.1002764","volume":"8","author":"B Murrell","year":"2012","unstructured":"Murrell, B. et al. Detecting individual sites subject to episodic diversifying selection. PLoS Genet. 8, e1002764 (2012).","journal-title":"PLoS Genet."},{"key":"BFsrep39458_CR57","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1093\/molbev\/mst030","volume":"30","author":"B Murrell","year":"2013","unstructured":"Murrell, B. et al. FUBAR: a fast, unconstrained bayesian approximation for inferring selection. Mol. Biol. Evol. 30, 1196\u20131205 (2013).","journal-title":"Mol. Biol. Evol."},{"key":"BFsrep39458_CR58","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1093\/molbev\/msi105","volume":"22","author":"SL Kosakovsky Pond","year":"2005","unstructured":"Kosakovsky Pond, S. L. & Frost, S. D. W. Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol. Biol. Evol. 22, 1208\u20131222 (2005).","journal-title":"Mol. Biol. Evol."},{"key":"BFsrep39458_CR59","doi-asserted-by":"crossref","unstructured":"Lemey, P. The phylogenetic handbook: a practical approach to phylogenetic analysis and hypothesis testing (Cambridge University Press, 2009).","DOI":"10.1017\/CBO9780511819049"},{"key":"BFsrep39458_CR60","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1093\/bioinformatics\/bti079","volume":"21","author":"SLK Pond","year":"2005","unstructured":"Pond, S. L. K. HyPhy: hypothesis testing using phylogenies. Bioinformatics 21, 676 (2005).","journal-title":"Bioinformatics"},{"key":"BFsrep39458_CR61","doi-asserted-by":"publisher","first-page":"e1002507","DOI":"10.1371\/journal.pcbi.1002507","volume":"8","author":"B Murrell","year":"2012","unstructured":"Murrell, B. et al. Modeling HIV-1 drug resistance as episodic directional selection. PLoS Comput. Biol. 8, e1002507 (2012).","journal-title":"PLoS Comput. Biol."},{"key":"BFsrep39458_CR62","doi-asserted-by":"publisher","first-page":"e9490","DOI":"10.1371\/journal.pone.0009490","volume":"5","author":"MN Price","year":"2010","unstructured":"Price, M. N., Dehal, P. S. & Arkin, A. P. FastTree 2\u2013approximately maximum-likelihood trees for large alignments. PLoS One 5, e9490 (2010).","journal-title":"PLoS One"},{"key":"BFsrep39458_CR63","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.virusres.2013.06.018","volume":"177","author":"M Ge","year":"2013","unstructured":"Ge, M. Epitope screening of the PCV2 Cap protein by use of a random peptide-displayed library and polyclonal antibody. Virus Res. 177, 103\u2013107 (2013).","journal-title":"Virus Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep39458.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39458","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39458.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T01:23:25Z","timestamp":1672881805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep39458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,19]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep39458"],"URL":"https:\/\/doi.org\/10.1038\/srep39458","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,19]]},"assertion":[{"value":"16 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39458"}}