Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014

Chikungunya virus (CHIKV) is considered a public health problem due to its rapid spread and high morbidity. This study aimed to determine the genetic diversity and phylogenetic relationships of CHIKVs in Colombia. A descriptive and retrospective study was carried out using sera of patients infected...

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Autores:
Villero Wolf, Yeneiris Karina
Mattar Velilla, Ameth Salim
Puerta González, Andrés
Arrieta Bernate, Germán Javier
Muskus, Carlos
Hoyos Lopez, Richard Onalbi
Pinzón, Hernando
Peláez Carvajal, Dioselina
Tipo de recurso:
Article of investigation
Fecha de publicación:
2019
Institución:
Corporación Universitaria del Caribe - CECAR
Repositorio:
Repositorio Digital CECAR
Idioma:
eng
OAI Identifier:
oai:repositorio.cecar.edu.co:cecar/10868
Acceso en línea:
https://repositorio.cecar.edu.co/handle/cecar/10868
Palabra clave:
Chikungunya virus
Morbidity
Public health problem d
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openAccess
License
Derechos reservados - Corporación Universitaria de Caribe - CECAR
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oai_identifier_str oai:repositorio.cecar.edu.co:cecar/10868
network_acronym_str RepoCECAR2
network_name_str Repositorio Digital CECAR
repository_id_str
dc.title.none.fl_str_mv Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014
title Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014
spellingShingle Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014
Chikungunya virus
Morbidity
Public health problem d
title_short Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014
title_full Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014
title_fullStr Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014
title_full_unstemmed Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014
title_sort Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014
dc.creator.fl_str_mv Villero Wolf, Yeneiris Karina
Mattar Velilla, Ameth Salim
Puerta González, Andrés
Arrieta Bernate, Germán Javier
Muskus, Carlos
Hoyos Lopez, Richard Onalbi
Pinzón, Hernando
Peláez Carvajal, Dioselina
dc.contributor.author.none.fl_str_mv Villero Wolf, Yeneiris Karina
Mattar Velilla, Ameth Salim
Puerta González, Andrés
Arrieta Bernate, Germán Javier
Muskus, Carlos
Hoyos Lopez, Richard Onalbi
Pinzón, Hernando
Peláez Carvajal, Dioselina
dc.contributor.corporatename.none.fl_str_mv Corporación Universitaria del caribe - CECAR
dc.contributor.researchgroup.none.fl_str_mv Salud Pública y Auditoría en Salud
dc.subject.proposal.none.fl_str_mv Chikungunya virus
Morbidity
Public health problem d
topic Chikungunya virus
Morbidity
Public health problem d
description Chikungunya virus (CHIKV) is considered a public health problem due to its rapid spread and high morbidity. This study aimed to determine the genetic diversity and phylogenetic relationships of CHIKVs in Colombia. A descriptive and retrospective study was carried out using sera of patients infected with Chikungunya during the outbreak in Colombia. The whole genomes of CHIKV (n=16) were sequenced with an Illumina Hi-seq 2500 and were assembled using the Iterative Virus Assembler software. A Bayesian inference phylogenetic analysis was carried out with 157 strains of worldwide origin. The Colombian CHIKV sequences were grouped in the Asian genotype; however, three independent phylogenetic subclades were observed, probably the result of three separate introductions from Panama, Nicaragua, and St. Barts. Each subclade showed several different non-synonymous mutations (nsP2-A153V; nsp2-Y543H; nsp2-G720A; nsP3-L458P; Capside R78Q), that may have functional consequences for CHIKV biology and pathogenesis. These same mutations may affect the efficacy of potential CHIKV vaccines.
publishDate 2019
dc.date.issued.none.fl_str_mv 2019
dc.date.accessioned.none.fl_str_mv 2025-09-04T20:20:44Z
dc.type.none.fl_str_mv Artículo de revista
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.content.none.fl_str_mv Text
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.redcol.none.fl_str_mv http://purl.org/redcol/resource_type/ART
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.none.fl_str_mv https://repositorio.cecar.edu.co/handle/cecar/10868
dc.identifier.eissn.none.fl_str_mv 2045-2322
url https://repositorio.cecar.edu.co/handle/cecar/10868
identifier_str_mv 2045-2322
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.citationendpage.none.fl_str_mv 11
dc.relation.citationstartpage.none.fl_str_mv 1
dc.relation.citationvolume.none.fl_str_mv Volumen 9
dc.relation.ispartofjournal.none.fl_str_mv Scientific Reports
dc.relation.references.none.fl_str_mv An, W., Ge, N., Cao, Y., Sun, J. & Jin, X. Recent progress on chikungunya virus research. Virologica Sinica 32, 441–453, https://doi. org/10.1007/s12250-017-4072-x (2017).
Tsetsarkin, K. A., Chen, R. & Weaver, S. C. Interspecies transmission and chikungunya virus emergence. Current opinion in virology 16, 143–150, https://doi.org/10.1016/j.coviro.2016.02.007 (2016).
Pan American Health Organization, World Health Organization. Number of reported cases of Chikungunya fever in the Americas: Epidemiological Week 1–52, 2014, https://www.paho.org/hq/index.php?option=com_topics&view=rdmore&cid=7928&item= chikungunya&cat=statistics&type=2014-7928&Itemid=40931&lang=en (2014).
de Lamballerie, X. et al. Chikungunya virus adapts to tiger mosquito via evolutionary convergence: a sign of things to come? Virology journal 5, 33, https://doi.org/10.1186/1743-422X-5-33 (2008).
Abraham, R. et al. Correlation of phylogenetic clade diversification and in vitro infectivity differences among Cosmopolitan genotype strains of Chikungunya virus. Infection, genetics and evolution 37, 174–184, https://doi.org/10.1016/j.meegid.2015.11.019 (2016).
Shragai, T., Tesla, B., Murdock, C. & Harrington, L. C. Zika and chikungunya: mosquito-borne viruses in a changing world. Annals of the New York Academy of Sciences 1399, 61–77, https://doi.org/10.1111/nyas.13306 (2017).
Sahadeo, N. S. D. et al. Understanding the evolution and spread of chikungunya virus in the Americas using complete genome sequences. Virus evolution 3, vex010, https://doi.org/10.1093/ve/vex010 (2017).
Chen, M. W. et al. Chikungunya virus nsP4 RNA-dependent RNA polymerase core domain displays detergent-sensitive primer extension and terminal adenylyltransferase activities. Antiviral research 143, 38–47, https://doi.org/10.1016/j.antiviral.2017.04.001 (2017).
Schwartz, O. & Albert, M. L. Biology and pathogenesis of chikungunya virus. Nature reviews. Microbiology 8, 491–500, https://doi. org/10.1038/nrmicro2368 (2010).
Yang, S., Fink, D., Hulse, A. & Pratt, R. D. Regulatory considerations in development of vaccines to prevent disease caused by Chikungunya virus. Vaccine 35, 4851–4858, https://doi.org/10.1016/j.vaccine.2017.07.065 (2017).
Vu, D. M., Jungkind, D. & Angelle Desiree, L. Chikungunya Virus. Clinics in laboratory medicine 37, 371–382, https://doi. org/10.1016/j.cll.2017.01.008 (2017).
Weber, C. et al. Identification of Functional Determinants in the Chikungunya Virus E2 Protein. PLoS neglected tropical diseases 11, e0005318, https://doi.org/10.1371/journal.pntd.0005318 (2017).
Méndez, N., Oviedo-Pastrana, M., Mattar, S., Caicedo-Castro, I. & Arrieta, G. Zika virus disease, microcephaly and Guillain-Barre syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017. Archives of public health=Archives belges de sante publique 75, 65, https://doi.org/10.1186/s13690-017-0233-5 (2017).
Laiton-Donato, K. et al. Phylogenetic analysis of Chikungunya virus in Colombia: Evidence of purifying selection in the E1 gene. Biomedica: revista del Instituto Nacional de Salud 36, 25–34, https://doi.org/10.7705/biomedica.v36i0.2990 (2015).
Pan American Healt Organization. Geographic Spread of Chikungunya in the Americas for december 2013–December 2017. http:// ais.paho.org/phip/viz/ed_chikungunya_amro.asp (2017).
Instituto Nacional de Salud. Comportamientos de los eventos de vigilancia en salud pública. Boletines epidemiológico 53 de 2014. https://www.ins.gov.co/buscador-eventos/BoletinEpidemiologico/2014%20Boletin%20epidemiologico%20semana%2053.pdf (2014).
Instituto Nacional de Salud. Comportamientos de los eventos de vigilancia en salud pública. Boletin epidemiológico 52 de 2015. https://www.ins.gov.co/buscador-eventos/BoletinEpidemiologico/2015%20Boletin%20epidemiologico%20Semana%2052.pdf (2015).
Instituto Nacional de Salud. Comportamientos de los eventos de vigilancia en salud pública. Boletin epidemiológico 52 de 2016; Boletin epidemiológico 52 de 2017; Boletin epidemiológico 17 de 2018. https://www.ins.gov.co/buscador-eventos/Paginas/VistaBoletin-Epidemilogico.aspx (2014).
Instituto Nacional de Salud. Comportamientos de los eventos de vigilancia en salud pública. Boletin epidemiológico 37 de 2014. https://www.ins.gov.co/buscador-eventos/BoletinEpidemiologico/2014%20Boletin%20epidemiologico%20semana%2037.pdf (2014).
Mattar, S. et al. Outbreak of Chikungunya virus in the north Caribbean area of Colombia: clinical presentation and phylogenetic analysis. Journal of infection in developing countries 9, 1126–1132, https://doi.org/10.3855/jidc.6670 (2015).
Volk, S. M. et al. Genome-scale phylogenetic analyses of chikungunya virus reveal independent emergences of recent epidemics and various evolutionary rates. Journal of virology 84, 6497–6504, https://doi.org/10.1128/JVI.01603-09 (2010).
Nunes, M. R. et al. Emergence and potential for spread of Chikungunya virus in Brazil. BMC medicine 13, 102, https://doi. org/10.1186/s12916-015-0348-x (2015).
Chen, R. et al. Comprehensive Genome Scale Phylogenetic Study Provides New Insights on the Global Expansion of Chikungunya Virus. Journal of virology 90, 10600–10611, https://doi.org/10.1128/JVI.01166-16 (2016).
Rodas, J. D. et al. Genetic Characterization of Northwestern Colombian Chikungunya Virus Strains from the 2014-2015 Epidemic. The American journal of tropical medicine and hygiene 95, 639–646, https://doi.org/10.4269/ajtmh.16-0091 (2016).
Carrillo-Hernandez, M. Y., Ruiz-Saenz, J., Villamizar, L. J., Gomez-Rangel, S. Y. & Martinez-Gutierrez, M. Co-circulation and simultaneous co-infection of dengue, chikungunya, and zika viruses in patients with febrile syndrome at the Colombian-Venezuelan border. BMC infectious diseases 18, 61, https://doi.org/10.1186/s12879-018-2976-1 (2018).
Pimentel, R., Skewes-Ramm, R. & Moya, J. Chikungunya en la República Dominicana: lecciones aprendidas en los primeros seis meses. Rev Panam Salud Publica 36, 336–341 (2014).
Instituto Nacional de Salud. Informe Final del Evento Chikungunya, Colombia 2014. http://www.ins.gov.co/buscador-eventos/ Informesdeevento/Chikungun%CC%83a%202014.pdf (2014).
Ministerio de Relaciones Exteriores. Boletin migratorio Julio del 2014. http://migracioncolombia.gov.co/index.php/ es/?option=com_content&view=article&id=718 (2014).
Carrera, J. P. et al. Unusual pattern of chikungunya virus epidemic in the Americas, the Panamanian experience. PLoS neglected tropical diseases 11, e0005338, https://doi.org/10.1371/journal.pntd.0005338 (2017).
Grillet, M. E. et al. Venezuela’s humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region. The Lancet Infectious Diseases, https://doi.org/10.1016/s1473-3099(18)30757-6 (2019).
Wang, C. et al. Chikungunya Virus Sequences Across the First Epidemic in Nicaragua, 2014–2015. The American journal of tropical medicine and hygiene 94, 400–403, https://doi.org/10.4269/ajtmh.15-0497 (2016).
Cherabuddi, K. et al. Zika and Chikungunya virus co-infection in a traveller returning from Colombia, 2016: virus isolation and genetic analysis. JMM case reports 3 (2016).
Ruiz-López, F. et al. Presence of Aedes (Stegomyia) aegypti (Linnaeus, 1762) and its natural infection with dengue virus at unrecorded heights in Colombia. Biomedica: revista del Instituto Nacional de Salud 36, 303–308 (2016).
Stapleford, K. A. et al. Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements. PLoS neglected tropical diseases 10, e0004402, https://doi.org/10.1371/journal.pntd.0004402 (2016).
Hawman, D. W. et al. Mutations in the E2 Glycoprotein and the 3′ Untranslated Region Enhance Chikungunya Virus Virulence in Mice. Journal of virology, https://doi.org/10.1128/JVI.00816-17 (2017).
Tsetsarkin, K. A. et al. Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes. PloS one 4, e6835, https://doi.org/10.1371/journal.pone.0006835 (2009).
Zouache, K. & Failloux, A.-B. Insect–pathogen interactions: contribution of viral adaptation to the emergence of vector-borne diseases, the example of chikungunya. Current Opinion in Insect Science 10, 14–21, https://doi.org/10.1016/j.cois.2015.04.010 (2015).
Tsetsarkin, K. A., Chen, R., Sherman, M. B. & Weaver, S. C. Chikungunya virus: evolution and genetic determinants of emergence. Current opinion in virology 1, 310–317, https://doi.org/10.1016/j.coviro.2011.07.004 (2011).
Republica de Colombia, Ministerio de Salud, Resolucion N° 008430 DE 1993. Por la cual se establecen las normas científicas, técnicas y administrativas para la investigación en salud (4 de octubre de 1993).
WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects. https://www.wma.net/wpcontent/uploads/2016/11/DoH-Oct2013-JAMA.pdf (2013).
Paternina-Caicedo, A. et al. Features of Dengue and Chikungunya Infections of Colombian Children under 24 Months of Age Admitted to the Emergency Department. Journal of tropical pediatrics 64, 31–37, https://doi.org/10.1093/tropej/fmx024 (2018).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120, https://doi.org/10.1093/bioinformatics/btu170 (2014).
Hunt, M. et al. IVA: accurate de novo assembly of RNA virus genomes. Bioinformatics 31, 2374–2376, https://doi.org/10.1093/ bioinformatics/btv120 (2015).
Edgar, R. C. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC bioinformatics 5, 113, https://doi.org/10.1186/1471-2105-5-113 (2004).
Kearse, M. et al. Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28, 1647–1649, https://doi.org/10.1093/bioinformatics/bts199 (2012).
Suchard, M. A. et al. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Virus evolution 4, vey016, https:// doi.org/10.1093/ve/vey016 (2018).
dc.rights.none.fl_str_mv Derechos reservados - Corporación Universitaria de Caribe - CECAR
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spelling Villero Wolf, Yeneiris KarinaMattar Velilla, Ameth SalimPuerta González, AndrésArrieta Bernate, Germán JavierMuskus, CarlosHoyos Lopez, Richard OnalbiPinzón, HernandoPeláez Carvajal, DioselinaCorporación Universitaria del caribe - CECARSalud Pública y Auditoría en Salud2025-09-04T20:20:44Z2019https://repositorio.cecar.edu.co/handle/cecar/108682045-2322Chikungunya virus (CHIKV) is considered a public health problem due to its rapid spread and high morbidity. This study aimed to determine the genetic diversity and phylogenetic relationships of CHIKVs in Colombia. A descriptive and retrospective study was carried out using sera of patients infected with Chikungunya during the outbreak in Colombia. The whole genomes of CHIKV (n=16) were sequenced with an Illumina Hi-seq 2500 and were assembled using the Iterative Virus Assembler software. A Bayesian inference phylogenetic analysis was carried out with 157 strains of worldwide origin. The Colombian CHIKV sequences were grouped in the Asian genotype; however, three independent phylogenetic subclades were observed, probably the result of three separate introductions from Panama, Nicaragua, and St. Barts. Each subclade showed several different non-synonymous mutations (nsP2-A153V; nsp2-Y543H; nsp2-G720A; nsP3-L458P; Capside R78Q), that may have functional consequences for CHIKV biology and pathogenesis. These same mutations may affect the efficacy of potential CHIKV vaccines.Auditoría en SalSalud Pública11 páginasapplication/pdfengDerechos reservados - Corporación Universitaria de Caribe - CECARhttps://creativecommons.org/licenses/by-nc/4.0/Atribución-NoComercial 4.0 Internacional (CC BY-NC 4.0)info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2https://doi.org/10.1038/s41598-019-45981-8Genomic epidemiology of Chikungunya virus in Colombia reveals genetic variability of strains and multiple geographic introductions in outbreak, 2014Artículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Colombia111Volumen 9Scientific ReportsAn, W., Ge, N., Cao, Y., Sun, J. & Jin, X. Recent progress on chikungunya virus research. Virologica Sinica 32, 441–453, https://doi. org/10.1007/s12250-017-4072-x (2017).Tsetsarkin, K. A., Chen, R. & Weaver, S. C. Interspecies transmission and chikungunya virus emergence. Current opinion in virology 16, 143–150, https://doi.org/10.1016/j.coviro.2016.02.007 (2016).Pan American Health Organization, World Health Organization. Number of reported cases of Chikungunya fever in the Americas: Epidemiological Week 1–52, 2014, https://www.paho.org/hq/index.php?option=com_topics&view=rdmore&cid=7928&item= chikungunya&cat=statistics&type=2014-7928&Itemid=40931&lang=en (2014).de Lamballerie, X. et al. Chikungunya virus adapts to tiger mosquito via evolutionary convergence: a sign of things to come? Virology journal 5, 33, https://doi.org/10.1186/1743-422X-5-33 (2008).Abraham, R. et al. Correlation of phylogenetic clade diversification and in vitro infectivity differences among Cosmopolitan genotype strains of Chikungunya virus. Infection, genetics and evolution 37, 174–184, https://doi.org/10.1016/j.meegid.2015.11.019 (2016).Shragai, T., Tesla, B., Murdock, C. & Harrington, L. C. Zika and chikungunya: mosquito-borne viruses in a changing world. Annals of the New York Academy of Sciences 1399, 61–77, https://doi.org/10.1111/nyas.13306 (2017).Sahadeo, N. S. D. et al. Understanding the evolution and spread of chikungunya virus in the Americas using complete genome sequences. Virus evolution 3, vex010, https://doi.org/10.1093/ve/vex010 (2017).Chen, M. W. et al. Chikungunya virus nsP4 RNA-dependent RNA polymerase core domain displays detergent-sensitive primer extension and terminal adenylyltransferase activities. Antiviral research 143, 38–47, https://doi.org/10.1016/j.antiviral.2017.04.001 (2017).Schwartz, O. & Albert, M. L. Biology and pathogenesis of chikungunya virus. Nature reviews. Microbiology 8, 491–500, https://doi. org/10.1038/nrmicro2368 (2010).Yang, S., Fink, D., Hulse, A. & Pratt, R. D. Regulatory considerations in development of vaccines to prevent disease caused by Chikungunya virus. Vaccine 35, 4851–4858, https://doi.org/10.1016/j.vaccine.2017.07.065 (2017).Vu, D. M., Jungkind, D. & Angelle Desiree, L. Chikungunya Virus. Clinics in laboratory medicine 37, 371–382, https://doi. org/10.1016/j.cll.2017.01.008 (2017).Weber, C. et al. Identification of Functional Determinants in the Chikungunya Virus E2 Protein. PLoS neglected tropical diseases 11, e0005318, https://doi.org/10.1371/journal.pntd.0005318 (2017).Méndez, N., Oviedo-Pastrana, M., Mattar, S., Caicedo-Castro, I. & Arrieta, G. Zika virus disease, microcephaly and Guillain-Barre syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017. Archives of public health=Archives belges de sante publique 75, 65, https://doi.org/10.1186/s13690-017-0233-5 (2017).Laiton-Donato, K. et al. Phylogenetic analysis of Chikungunya virus in Colombia: Evidence of purifying selection in the E1 gene. Biomedica: revista del Instituto Nacional de Salud 36, 25–34, https://doi.org/10.7705/biomedica.v36i0.2990 (2015).Pan American Healt Organization. Geographic Spread of Chikungunya in the Americas for december 2013–December 2017. http:// ais.paho.org/phip/viz/ed_chikungunya_amro.asp (2017).Instituto Nacional de Salud. Comportamientos de los eventos de vigilancia en salud pública. Boletines epidemiológico 53 de 2014. https://www.ins.gov.co/buscador-eventos/BoletinEpidemiologico/2014%20Boletin%20epidemiologico%20semana%2053.pdf (2014).Instituto Nacional de Salud. Comportamientos de los eventos de vigilancia en salud pública. Boletin epidemiológico 52 de 2015. https://www.ins.gov.co/buscador-eventos/BoletinEpidemiologico/2015%20Boletin%20epidemiologico%20Semana%2052.pdf (2015).Instituto Nacional de Salud. Comportamientos de los eventos de vigilancia en salud pública. Boletin epidemiológico 52 de 2016; Boletin epidemiológico 52 de 2017; Boletin epidemiológico 17 de 2018. https://www.ins.gov.co/buscador-eventos/Paginas/VistaBoletin-Epidemilogico.aspx (2014).Instituto Nacional de Salud. Comportamientos de los eventos de vigilancia en salud pública. Boletin epidemiológico 37 de 2014. https://www.ins.gov.co/buscador-eventos/BoletinEpidemiologico/2014%20Boletin%20epidemiologico%20semana%2037.pdf (2014).Mattar, S. et al. Outbreak of Chikungunya virus in the north Caribbean area of Colombia: clinical presentation and phylogenetic analysis. Journal of infection in developing countries 9, 1126–1132, https://doi.org/10.3855/jidc.6670 (2015).Volk, S. M. et al. Genome-scale phylogenetic analyses of chikungunya virus reveal independent emergences of recent epidemics and various evolutionary rates. Journal of virology 84, 6497–6504, https://doi.org/10.1128/JVI.01603-09 (2010).Nunes, M. R. et al. Emergence and potential for spread of Chikungunya virus in Brazil. BMC medicine 13, 102, https://doi. org/10.1186/s12916-015-0348-x (2015).Chen, R. et al. Comprehensive Genome Scale Phylogenetic Study Provides New Insights on the Global Expansion of Chikungunya Virus. Journal of virology 90, 10600–10611, https://doi.org/10.1128/JVI.01166-16 (2016).Rodas, J. D. et al. Genetic Characterization of Northwestern Colombian Chikungunya Virus Strains from the 2014-2015 Epidemic. The American journal of tropical medicine and hygiene 95, 639–646, https://doi.org/10.4269/ajtmh.16-0091 (2016).Carrillo-Hernandez, M. Y., Ruiz-Saenz, J., Villamizar, L. J., Gomez-Rangel, S. Y. & Martinez-Gutierrez, M. Co-circulation and simultaneous co-infection of dengue, chikungunya, and zika viruses in patients with febrile syndrome at the Colombian-Venezuelan border. BMC infectious diseases 18, 61, https://doi.org/10.1186/s12879-018-2976-1 (2018).Pimentel, R., Skewes-Ramm, R. & Moya, J. Chikungunya en la República Dominicana: lecciones aprendidas en los primeros seis meses. Rev Panam Salud Publica 36, 336–341 (2014).Instituto Nacional de Salud. Informe Final del Evento Chikungunya, Colombia 2014. http://www.ins.gov.co/buscador-eventos/ Informesdeevento/Chikungun%CC%83a%202014.pdf (2014).Ministerio de Relaciones Exteriores. Boletin migratorio Julio del 2014. http://migracioncolombia.gov.co/index.php/ es/?option=com_content&view=article&id=718 (2014).Carrera, J. P. et al. Unusual pattern of chikungunya virus epidemic in the Americas, the Panamanian experience. PLoS neglected tropical diseases 11, e0005338, https://doi.org/10.1371/journal.pntd.0005338 (2017).Grillet, M. E. et al. Venezuela’s humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region. The Lancet Infectious Diseases, https://doi.org/10.1016/s1473-3099(18)30757-6 (2019).Wang, C. et al. Chikungunya Virus Sequences Across the First Epidemic in Nicaragua, 2014–2015. The American journal of tropical medicine and hygiene 94, 400–403, https://doi.org/10.4269/ajtmh.15-0497 (2016).Cherabuddi, K. et al. Zika and Chikungunya virus co-infection in a traveller returning from Colombia, 2016: virus isolation and genetic analysis. JMM case reports 3 (2016).Ruiz-López, F. et al. Presence of Aedes (Stegomyia) aegypti (Linnaeus, 1762) and its natural infection with dengue virus at unrecorded heights in Colombia. Biomedica: revista del Instituto Nacional de Salud 36, 303–308 (2016).Stapleford, K. A. et al. Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements. PLoS neglected tropical diseases 10, e0004402, https://doi.org/10.1371/journal.pntd.0004402 (2016).Hawman, D. W. et al. Mutations in the E2 Glycoprotein and the 3′ Untranslated Region Enhance Chikungunya Virus Virulence in Mice. Journal of virology, https://doi.org/10.1128/JVI.00816-17 (2017).Tsetsarkin, K. A. et al. Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes. PloS one 4, e6835, https://doi.org/10.1371/journal.pone.0006835 (2009).Zouache, K. & Failloux, A.-B. Insect–pathogen interactions: contribution of viral adaptation to the emergence of vector-borne diseases, the example of chikungunya. Current Opinion in Insect Science 10, 14–21, https://doi.org/10.1016/j.cois.2015.04.010 (2015).Tsetsarkin, K. A., Chen, R., Sherman, M. B. & Weaver, S. C. Chikungunya virus: evolution and genetic determinants of emergence. Current opinion in virology 1, 310–317, https://doi.org/10.1016/j.coviro.2011.07.004 (2011).Republica de Colombia, Ministerio de Salud, Resolucion N° 008430 DE 1993. Por la cual se establecen las normas científicas, técnicas y administrativas para la investigación en salud (4 de octubre de 1993).WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects. https://www.wma.net/wpcontent/uploads/2016/11/DoH-Oct2013-JAMA.pdf (2013).Paternina-Caicedo, A. et al. Features of Dengue and Chikungunya Infections of Colombian Children under 24 Months of Age Admitted to the Emergency Department. Journal of tropical pediatrics 64, 31–37, https://doi.org/10.1093/tropej/fmx024 (2018).Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120, https://doi.org/10.1093/bioinformatics/btu170 (2014).Hunt, M. et al. IVA: accurate de novo assembly of RNA virus genomes. Bioinformatics 31, 2374–2376, https://doi.org/10.1093/ bioinformatics/btv120 (2015).Edgar, R. C. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC bioinformatics 5, 113, https://doi.org/10.1186/1471-2105-5-113 (2004).Kearse, M. et al. Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28, 1647–1649, https://doi.org/10.1093/bioinformatics/bts199 (2012).Suchard, M. A. et al. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. 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9ycG9yYWRhIGVuIGxhcyBPYnJhcyBDb2xlY3RpdmFzLgpiLiBEaXN0cmlidWlyIGNvcGlhcyBvIGZvbm9ncmFtYXMgZGUgbGFzIE9icmFzLCBleGhpYmlybGFzIHDDumJsaWNhbWVudGUsIGVqZWN1dGFybGFzIHDDumJsaWNhbWVudGUgeS9vIHBvbmVybGFzIGEgZGlzcG9zaWNpw7NuIHDDumJsaWNhLCBpbmNsdXnDqW5kb2xhcyBjb21vIGluY29ycG9yYWRhcyBlbiBPYnJhcyBDb2xlY3RpdmFzLCBzZWfDum4gY29ycmVzcG9uZGEuCmMuIERpc3RyaWJ1aXIgY29waWFzIGRlIGxhcyBPYnJhcyBEZXJpdmFkYXMgcXVlIHNlIGdlbmVyZW4sIGV4aGliaXJsYXMgcMO6YmxpY2FtZW50ZSwgZWplY3V0YXJsYXMgcMO6YmxpY2FtZW50ZSB5L28gcG9uZXJsYXMgYSBkaXNwb3NpY2nDs24gcMO6YmxpY2EuCgpMb3MgZGVyZWNob3MgbWVuY2lvbmFkb3MgYW50ZXJpb3JtZW50ZSBwdWVkZW4gc2VyIGVqZXJjaWRvcyBlbiB0b2RvcyBsb3MgbWVkaW9zIHkgZm9ybWF0b3MsIGFjdHVhbG1lbnRlIGNvbm9jaWRvcyBvIHF1ZSBzZSBpbnZlbnRlbiBlbiBlbCBmdXR1cm8uIExvcyBkZXJlY2hvcyBhbnRlcyBtZW5jaW9uYWRvcyBpbmNsdXllbiBlbCBkZXJlY2hvIGEgcmVhbGl6YXIgZGljaGFzIG1vZGlmaWNhY2lvbmVzIGVuIGxhIG1lZGlkYSBxdWUgc2VhbiB0w6ljbmljYW1lbnRlIG5lY2VzYXJpYXMgcGFyYSBlamVyY2VyIGxvcyBkZXJlY2hvcyBlbiBvdHJvIG1lZGlvIG8gZm9ybWF0b3MsIHBlcm8gZGUgb3RyYSBtYW5lcmEgdXN0ZWQgbm8gZXN0w6EgYXV0b3JpemFkbyBwYXJhIHJlYWxpemFyIG9icmFzIGRlcml2YWRhcy4gVG9kb3MgbG9zIGRlcmVjaG9zIG5vIG90b3JnYWRvcyBleHByZXNhbWVudGUgcG9yIGVsIExpY2VuY2lhbnRlIHF1ZWRhbiBwb3IgZXN0ZSBtZWRpbyByZXNlcnZhZG9zLCBpbmNsdXllbmRvIHBlcm8gc2luIGxpbWl0YXJzZSBhIGFxdWVsbG9zIHF1ZSBzZSBtZW5jaW9uYW4gZW4gbGFzIHNlY2Npb25lcyA0KGQpIHkgNChlKS4KICAgIAo0LiBSZXN0cmljY2lvbmVzLgpMYSBsaWNlbmNpYSBvdG9yZ2FkYSBlbiBsYSBhbnRlcmlvciBTZWNjacOzbiAzIGVzdMOhIGV4cHJlc2FtZW50ZSBzdWpldGEgeSBsaW1pdGFkYSBwb3IgbGFzIHNpZ3VpZW50ZXMgcmVzdHJpY2Npb25lczoKYS4gVXN0ZWQgcHVlZGUgZGlzdHJpYnVpciwgZXhoaWJpciBww7pibGljYW1lbnRlLCBlamVjdXRhciBww7pibGljYW1lbnRlLCBvIHBvbmVyIGEgZGlzcG9zaWNpw7NuIHDDumJsaWNhIGxhIE9icmEgc8OzbG8gYmFqbyBsYXMgY29uZGljaW9uZXMgZGUgZXN0YSBMaWNlbmNpYSwgeSBVc3RlZCBkZWJlIGluY2x1aXIgdW5hIGNvcGlhIGRlIGVzdGEgbGljZW5jaWEgbyBkZWwgSWRlbnRpZmljYWRvciBVbml2ZXJzYWwgZGUgUmVjdXJzb3MgZGUgbGEgbWlzbWEgY29uIGNhZGEgY29waWEgZGUgbGEgT2JyYSBxdWUgZGlzdHJpYnV5YSwgZXhoaWJhIHDDumJsaWNhbWVudGUsIGVqZWN1dGUgcMO6YmxpY2FtZW50ZSBvIHBvbmdhIGEgZGlzcG9zaWNpw7NuIHDDumJsaWNhLiBObyBlcyBwb3NpYmxlIG9mcmVjZXIgbyBpbXBvbmVyIG5pbmd1bmEgY29uZGljacOzbiBzb2JyZSBsYSBPYnJhIHF1ZSBhbHRlcmUgbyBsaW1pdGUgbGFzIGNvbmRpY2lvbmVzIGRlIGVzdGEgTGljZW5jaWEgbyBlbCBlamVyY2ljaW8gZGUgbG9zIGRlcmVjaG9zIGRlIGxvcyBkZXN0aW5hdGFyaW9zIG90b3JnYWRvcyBlbiBlc3RlIGRvY3VtZW50by4gTm8gZXMgcG9zaWJsZSBzdWJsaWNlbmNpYXIgbGEgT2JyYS4gVXN0ZWQgZGViZSBtYW50ZW5lciBpbnRhY3RvcyB0b2RvcyBsb3MgYXZpc29zIHF1ZSBoYWdhbiByZWZlcmVuY2lhIGEgZXN0YSBMaWNlbmNpYSB5IGEgbGEgY2zDoXVzdWxhIGRlIGxpbWl0YWNpw7NuIGRlIGdhcmFudMOtYXMuIFVzdGVkIG5vIHB1ZWRlIGRpc3RyaWJ1aXIsIGV4aGliaXIgcMO6YmxpY2FtZW50ZSwgZWplY3V0YXIgcMO6YmxpY2FtZW50ZSwgbyBwb25lciBhIGRpc3Bvc2ljacOzbiBww7pibGljYSBsYSBPYnJhIGNvbiBhbGd1bmEgbWVkaWRhIHRlY25vbMOzZ2ljYSBxdWUgY29udHJvbGUgZWwgYWNjZXNvIG8gbGEgdXRpbGl6YWNpw7NuIGRlIGVsbGEgZGUgdW5hIGZvcm1hIHF1ZSBzZWEgaW5jb25zaXN0ZW50ZSBjb24gbGFzIGNvbmRpY2lvbmVzIGRlIGVzdGEgTGljZW5jaWEuIExvIGFudGVyaW9yIHNlIGFwbGljYSBhIGxhIE9icmEgaW5jb3Jwb3JhZGEgYSB1bmEgT2JyYSBDb2xlY3RpdmEsIHBlcm8gZXN0byBubyBleGlnZSBxdWUgbGEgT2JyYSBDb2xlY3RpdmEgYXBhcnRlIGRlIGxhIG9icmEgbWlzbWEgcXVlZGUgc3VqZXRhIGEgbGFzIGNvbmRpY2lvbmVzIGRlIGVzdGEgTGljZW5jaWEuIFNpIFVzdGVkIGNyZWEgdW5hIE9icmEgQ29sZWN0aXZhLCBwcmV2aW8gYXZpc28gZGUgY3VhbHF1aWVyIExpY2VuY2lhbnRlIGRlYmUsIGVuIGxhIG1lZGlkYSBkZSBsbyBwb3NpYmxlLCBlbGltaW5hciBkZSBsYSBPYnJhIENvbGVjdGl2YSBjdWFscXVpZXIgcmVmZXJlbmNpYSBhIGRpY2hvIExpY2VuY2lhbnRlIG8gYWwgQXV0b3IgT3JpZ2luYWwsIHNlZ8O6biBsbyBzb2xpY2l0YWRvIHBvciBlbCBMaWNlbmNpYW50ZSB5IGNvbmZvcm1lIGxvIGV4aWdlIGxhIGNsw6F1c3VsYSA0KGMpLgpiLiBVc3RlZCBubyBwdWVkZSBlamVyY2VyIG5pbmd1bm8gZGUgbG9zIGRlcmVjaG9zIHF1ZSBsZSBoYW4gc2lkbyBvdG9yZ2Fkb3MgZW4gbGEgU2VjY2nDs24gMyBwcmVjZWRlbnRlIGRlIG1vZG8gcXVlIGVzdMOpbiBwcmluY2lwYWxtZW50ZSBkZXN0aW5hZG9zIG8gZGlyZWN0YW1lbnRlIGRpcmlnaWRvcyBhIGNvbnNlZ3VpciB1biBwcm92ZWNobyBjb21lcmNpYWwgbyB1bmEgY29tcGVuc2FjacOzbiBtb25ldGFyaWEgcHJpdmFkYS4gRWwgaW50ZXJjYW1iaW8gZGUgbGEgT2JyYSBwb3Igb3RyYXMgb2JyYXMgcHJvdGVnaWRhcyBwb3IgZGVyZWNob3MgZGUgYXV0b3IsIHlhIHNlYSBhIHRyYXbDqXMgZGUgdW4gc2lzdGVtYSBwYXJhIGNvbXBhcnRpciBhcmNoaXZvcyBkaWdpdGFsZXMgKGRpZ2l0YWwgZmlsZS1zaGFyaW5nKSBvIGRlIGN1YWxxdWllciBvdHJhIG1hbmVyYSBubyBzZXLDoSBjb25zaWRlcmFkbyBjb21vIGVzdGFyIGRlc3RpbmFkbyBwcmluY2lwYWxtZW50ZSBvIGRpcmlnaWRvIGRpcmVjdGFtZW50ZSBhIGNvbnNlZ3VpciB1biBwcm92ZWNobyBjb21lcmNpYWwgbyB1bmEgY29tcGVuc2FjacOzbiBtb25ldGFyaWEgcHJpdmFkYSwgc2llbXByZSBxdWUgbm8gc2UgcmVhbGljZSB1biBwYWdvIG1lZGlhbnRlIHVuYSBjb21wZW5zYWNpw7NuIG1vbmV0YXJpYSBlbiByZWxhY2nDs24gY29uIGVsIGludGVyY2FtYmlvIGRlIG9icmFzIHByb3RlZ2lkYXMgcG9yIGVsIGRlcmVjaG8gZGUgYXV0b3IuCmMuIFNpIHVzdGVkIGRpc3RyaWJ1eWUsIGV4aGliZSBww7pibGljYW1lbnRlLCBlamVjdXRhIHDDumJsaWNhbWVudGUgbyBlamVjdXRhIHDDumJsaWNhbWVudGUgZW4gZm9ybWEgZGlnaXRhbCBsYSBPYnJhIG8gY3VhbHF1aWVyIE9icmEgRGVyaXZhZGEgdSBPYnJhIENvbGVjdGl2YSwgVXN0ZWQgZGViZSBtYW50ZW5lciBpbnRhY3RhIHRvZGEgbGEgaW5mb3JtYWNpw7NuIGRlIGRlcmVjaG8gZGUgYXV0b3IgZGUgbGEgT2JyYSB5IHByb3BvcmNpb25hciwgZGUgZm9ybWEgcmF6b25hYmxlIHNlZ8O6biBlbCBtZWRpbyBvIG1hbmVyYSBxdWUgVXN0ZWQgZXN0w6kgdXRpbGl6YW5kbzogKGkpIGVsIG5vbWJyZSBkZWwgQXV0b3IgT3JpZ2luYWwgc2kgZXN0w6EgcHJvdmlzdG8gKG8gc2V1ZMOzbmltbywgc2kgZnVlcmUgYXBsaWNhYmxlKSwgeS9vIChpaSkgZWwgbm9tYnJlIGRlIGxhIHBhcnRlIG8gbGFzIHBhcnRlcyBxdWUgZWwgQXV0b3IgT3JpZ2luYWwgeS9vIGVsIExpY2VuY2lhbnRlIGh1YmllcmVuIGRlc2lnbmFkbyBwYXJhIGxhIGF0cmlidWNpw7NuICh2LmcuLCB1biBpbnN0aXR1dG8gcGF0cm9jaW5hZG9yLCBlZGl0b3JpYWwsIHB1YmxpY2FjacOzbikgZW4gbGEgaW5mb3JtYWNpw7NuIGRlIGxvcyBkZXJlY2hvcyBkZSBhdXRvciBkZWwgTGljZW5jaWFudGUsIHTDqXJtaW5vcyBkZSBzZXJ2aWNpb3MgbyBkZSBvdHJhcyBmb3JtYXMgcmF6b25hYmxlczsgZWwgdMOtdHVsbyBkZSBsYSBPYnJhIHNpIGVzdMOhIHByb3Zpc3RvOyBlbiBsYSBtZWRpZGEgZGUgbG8gcmF6b25hYmxlbWVudGUgZmFjdGlibGUgeSwgc2kgZXN0w6EgcHJvdmlzdG8sIGVsIElkZW50aWZpY2Fkb3IgVW5pZm9ybWUgZGUgUmVjdXJzb3MgKFVuaWZvcm0gUmVzb3VyY2UgSWRlbnRpZmllcikgcXVlIGVsIExpY2VuY2lhbnRlIGVzcGVjaWZpY2EgcGFyYSBzZXIgYXNvY2lhZG8gY29uIGxhIE9icmEsIHNhbHZvIHF1ZSB0YWwgVVJJIG5vIHNlIHJlZmllcmEgYSBsYSBub3RhIHNvYnJlIGxvcyBkZXJlY2hvcyBkZSBhdXRvciBvIGEgbGEgaW5mb3JtYWNpw7NuIHNvYnJlIGVsIGxpY2VuY2lhbWllbnRvIGRlIGxhIE9icmE7IHkgZW4gZWwgY2FzbyBkZSB1bmEgT2JyYSBEZXJpdmFkYSwgYXRyaWJ1aXIgZWwgY3LDqWRpdG8gaWRlbnRpZmljYW5kbyBlbCB1c28gZGUgbGEgT2JyYSBlbiBsYSBPYnJhIERlcml2YWRhICh2LmcuLCAiVHJhZHVjY2nDs24gRnJhbmNlc2EgZGUgbGEgT2JyYSBkZWwgQXV0b3IgT3JpZ2luYWwsIiBvICJHdWnDs24gQ2luZW1hdG9ncsOhZmljbyBiYXNhZG8gZW4gbGEgT2JyYSBvcmlnaW5hbCBkZWwgQXV0b3IgT3JpZ2luYWwiKS4gVGFsIGNyw6lkaXRvIHB1ZWRlIHNlciBpbXBsZW1lbnRhZG8gZGUgY3VhbHF1aWVyIGZvcm1hIHJhem9uYWJsZTsgZW4gZWwgY2Fzbywgc2luIGVtYmFyZ28sIGRlIE9icmFzIERlcml2YWRhcyB1IE9icmFzIENvbGVjdGl2YXMsIHRhbCBjcsOpZGl0byBhcGFyZWNlcsOhLCBjb21vIG3DrW5pbW8sIGRvbmRlIGFwYXJlY2UgZWwgY3LDqWRpdG8gZGUgY3VhbHF1aWVyIG90cm8gYXV0b3IgY29tcGFyYWJsZSB5IGRlIHVuYSBtYW5lcmEsIGFsIG1lbm9zLCB0YW4gZGVzdGFjYWRhIGNvbW8gZWwgY3LDqWRpdG8gZGUgb3RybyBhdXRvciBjb21wYXJhYmxlLiAgCmQuIFBhcmEgZXZpdGFyIHRvZGEgY29uZnVzacOzbiwgZWwgTGljZW5jaWFudGUgYWNsYXJhIHF1ZSwgY3VhbmRvIGxhIG9icmEgZXMgdW5hIGNvbXBvc2ljacOzbiBtdXNpY2FsOgoKaS4gUmVnYWzDrWFzIHBvciBpbnRlcnByZXRhY2nDs24geSBlamVjdWNpw7NuIGJham8gbGljZW5jaWFzIGdlbmVyYWxlcy4gRWwgTGljZW5jaWFudGUgc2UgcmVzZXJ2YSBlbCBkZXJlY2hvIGV4Y2x1c2l2byBkZSBhdXRvcml6YXIgbGEgZWplY3VjacOzbiBww7pibGljYSBvIGxhIGVqZWN1Y2nDs24gcMO6YmxpY2EgZGlnaXRhbCBkZSBsYSBvYnJhIHkgZGUgcmVjb2xlY3Rhciwgc2VhIGluZGl2aWR1YWxtZW50ZSBvIGEgdHJhdsOpcyBkZSB1bmEgc29jaWVkYWQgZGUgZ2VzdGnDs24gY29sZWN0aXZhIGRlIGRlcmVjaG9zIGRlIGF1dG9yIHkgZGVyZWNob3MgY29uZXhvcyAocG9yIGVqZW1wbG8sIFNBWUNPKSwgbGFzIHJlZ2Fsw61hcyBwb3IgbGEgZWplY3VjacOzbiBww7pibGljYSBvIHBvciBsYSBlamVjdWNpw7NuIHDDumJsaWNhIGRpZ2l0YWwgZGUgbGEgb2JyYSAocG9yIGVqZW1wbG8gV2ViY2FzdCkgbGljZW5jaWFkYSBiYWpvIGxpY2VuY2lhcyBnZW5lcmFsZXMsIHNpIGxhIGludGVycHJldGFjacOzbiBvIGVqZWN1Y2nDs24gZGUgbGEgb2JyYSBlc3TDoSBwcmltb3JkaWFsbWVudGUgb3JpZW50YWRhIHBvciBvIGRpcmlnaWRhIGEgbGEgb2J0ZW5jacOzbiBkZSB1bmEgdmVudGFqYSBjb21lcmNpYWwgbyB1bmEgY29tcGVuc2FjacOzbiBtb25ldGFyaWEgcHJpdmFkYS4KaWkuIFJlZ2Fsw61hcyBwb3IgRm9ub2dyYW1hcy4gRWwgTGljZW5jaWFudGUgc2UgcmVzZXJ2YSBlbCBkZXJlY2hvIGV4Y2x1c2l2byBkZSByZWNvbGVjdGFyLCBpbmRpdmlkdWFsbWVudGUgbyBhIHRyYXbDqXMgZGUgdW5hIHNvY2llZGFkIGRlIGdlc3Rpw7NuIGNvbGVjdGl2YSBkZSBkZXJlY2hvcyBkZSBhdXRvciB5IGRlcmVjaG9zIGNvbmV4b3MgKHBvciBlamVtcGxvLCBsb3MgY29uc2FncmFkb3MgcG9yIGxhIFNBWUNPKSwgdW5hIGFnZW5jaWEgZGUgZGVyZWNob3MgbXVzaWNhbGVzIG8gYWxnw7puIGFnZW50ZSBkZXNpZ25hZG8sIGxhcyByZWdhbMOtYXMgcG9yIGN1YWxxdWllciBmb25vZ3JhbWEgcXVlIFVzdGVkIGNyZWUgYSBwYXJ0aXIgZGUgbGEgb2JyYSAo4oCcdmVyc2nDs24gY292ZXLigJ0pIHkgZGlzdHJpYnV5YSwgZW4gbG9zIHTDqXJtaW5vcyBkZWwgcsOpZ2ltZW4gZGUgZGVyZWNob3MgZGUgYXV0b3IsIHNpIGxhIGNyZWFjacOzbiBvIGRpc3RyaWJ1Y2nDs24gZGUgZXNhIHZlcnNpw7NuIGNvdmVyIGVzdMOhIHByaW1vcmRpYWxtZW50ZSBkZXN0aW5hZGEgbyBkaXJpZ2lkYSBhIG9idGVuZXIgdW5hIHZlbnRhamEgY29tZXJjaWFsIG8gdW5hIGNvbXBlbnNhY2nDs24gbW9uZXRhcmlhIHByaXZhZGEuCiAgICAgIAplLiBHZXN0acOzbiBkZSBEZXJlY2hvcyBkZSBBdXRvciBzb2JyZSBJbnRlcnByZXRhY2lvbmVzIHkgRWplY3VjaW9uZXMgRGlnaXRhbGVzIChXZWJDYXN0aW5nKS4gUGFyYSBldml0YXIgdG9kYSBjb25mdXNpw7NuLCBlbCBMaWNlbmNpYW50ZSBhY2xhcmEgcXVlLCBjdWFuZG8gbGEgb2JyYSBzZWEgdW4gZm9ub2dyYW1hLCBlbCBMaWNlbmNpYW50ZSBzZSByZXNlcnZhIGVsIGRlcmVjaG8gZXhjbHVzaXZvIGRlIGF1dG9yaXphciBsYSBlamVjdWNpw7NuIHDDumJsaWNhIGRpZ2l0YWwgZGUgbGEgb2JyYSAocG9yIGVqZW1wbG8sIHdlYmNhc3QpIHkgZGUgcmVjb2xlY3RhciwgaW5kaXZpZHVhbG1lbnRlIG8gYSB0cmF2w6lzIGRlIHVuYSBzb2NpZWRhZCBkZSBnZXN0acOzbiBjb2xlY3RpdmEgZGUgZGVyZWNob3MgZGUgYXV0b3IgeSBkZXJlY2hvcyBjb25leG9zIChwb3IgZWplbXBsbywgQUNJTlBSTyksIGxhcyByZWdhbMOtYXMgcG9yIGxhIGVqZWN1Y2nDs24gcMO6YmxpY2EgZGlnaXRhbCBkZSBsYSBvYnJhIChwb3IgZWplbXBsbywgd2ViY2FzdCksIHN1amV0YSBhIGxhcyBkaXNwb3NpY2lvbmVzIGFwbGljYWJsZXMgZGVsIHLDqWdpbWVuIGRlIERlcmVjaG8gZGUgQXV0b3IsIHNpIGVzdGEgZWplY3VjacOzbiBww7pibGljYSBkaWdpdGFsIGVzdMOhIHByaW1vcmRpYWxtZW50ZSBkaXJpZ2lkYSBhIG9idGVuZXIgdW5hIHZlbnRhamEgY29tZXJjaWFsIG8gdW5hIGNvbXBlbnNhY2nDs24gbW9uZXRhcmlhIHByaXZhZGEuCiAgCjUuIFJlcHJlc2VudGFjaW9uZXMsIEdhcmFudMOtYXMgeSBMaW1pdGFjaW9uZXMgZGUgUmVzcG9uc2FiaWxpZGFkLgpBIE1FTk9TIFFVRSBMQVMgUEFSVEVTIExPIEFDT1JEQVJBTiBERSBPVFJBIEZPUk1BIFBPUiBFU0NSSVRPLCBFTCBMSUNFTkNJQU5URSBPRlJFQ0UgTEEgT0JSQSAoRU4gRUwgRVNUQURPIEVOIEVMIFFVRSBTRSBFTkNVRU5UUkEpIOKAnFRBTCBDVUFM4oCdLCBTSU4gQlJJTkRBUiBHQVJBTlTDjUFTIERFIENMQVNFIEFMR1VOQSBSRVNQRUNUTyBERSBMQSBPQlJBLCBZQSBTRUEgRVhQUkVTQSwgSU1QTMONQ0lUQSwgTEVHQUwgTyBDVUFMUVVJRVJBIE9UUkEsIElOQ0xVWUVORE8sIFNJTiBMSU1JVEFSU0UgQSBFTExBUywgR0FSQU5Uw41BUyBERSBUSVRVTEFSSURBRCwgQ09NRVJDSUFCSUxJREFELCBBREFQVEFCSUxJREFEIE8gQURFQ1VBQ0nDk04gQSBQUk9Qw5NTSVRPIERFVEVSTUlOQURPLCBBVVNFTkNJQSBERSBJTkZSQUNDScOTTiwgREUgQVVTRU5DSUEgREUgREVGRUNUT1MgTEFURU5URVMgTyBERSBPVFJPIFRJUE8sIE8gTEEgUFJFU0VOQ0lBIE8gQVVTRU5DSUEgREUgRVJST1JFUywgU0VBTiBPIE5PIERFU0NVQlJJQkxFUyAoUFVFREFOIE8gTk8gU0VSIEVTVE9TIERFU0NVQklFUlRPUykuIEFMR1VOQVMgSlVSSVNESUNDSU9ORVMgTk8gUEVSTUlURU4gTEEgRVhDTFVTScOTTiBERSBHQVJBTlTDjUFTIElNUEzDjUNJVEFTLCBFTiBDVVlPIENBU08gRVNUQSBFWENMVVNJw5NOIFBVRURFIE5PIEFQTElDQVJTRSBBIFVTVEVELgogIAo2LiBMaW1pdGFjacOzbiBkZSByZXNwb25zYWJpbGlkYWQuCkEgTUVOT1MgUVVFIExPIEVYSUpBIEVYUFJFU0FNRU5URSBMQSBMRVkgQVBMSUNBQkxFLCBFTCBMSUNFTkNJQU5URSBOTyBTRVLDgSBSRVNQT05TQUJMRSBBTlRFIFVTVEVEIFBPUiBEQcORTyBBTEdVTk8sIFNFQSBQT1IgUkVTUE9OU0FCSUxJREFEIEVYVFJBQ09OVFJBQ1RVQUwsIFBSRUNPTlRSQUNUVUFMIE8gQ09OVFJBQ1RVQUwsIE9CSkVUSVZBIE8gU1VCSkVUSVZBLCBTRSBUUkFURSBERSBEQcORT1MgTU9SQUxFUyBPIFBBVFJJTU9OSUFMRVMsIERJUkVDVE9TIE8gSU5ESVJFQ1RPUywgUFJFVklTVE9TIE8gSU1QUkVWSVNUT1MgUFJPRFVDSURPUyBQT1IgRUwgVVNPIERFIEVTVEEgTElDRU5DSUEgTyBERSBMQSBPQlJBLCBBVU4gQ1VBTkRPIEVMIExJQ0VOQ0lBTlRFIEhBWUEgU0lETyBBRFZFUlRJRE8gREUgTEEgUE9TSUJJTElEQUQgREUgRElDSE9TIERBw5FPUy4gQUxHVU5BUyBMRVlFUyBOTyBQRVJNSVRFTiBMQSBFWENMVVNJw5NOIERFIENJRVJUQSBSRVNQT05TQUJJTElEQUQsIEVOIENVWU8gQ0FTTyBFU1RBIEVYQ0xVU0nDk04gUFVFREUgTk8gQVBMSUNBUlNFIEEgVVNURUQuCiAgCjcuIFTDqXJtaW5vLgkKYS4gRXN0YSBMaWNlbmNpYSB5IGxvcyBkZXJlY2hvcyBvdG9yZ2Fkb3MgZW4gdmlydHVkIGRlIGVsbGEgdGVybWluYXLDoW4gYXV0b23DoXRpY2FtZW50ZSBzaSBVc3RlZCBpbmZyaW5nZSBhbGd1bmEgY29uZGljacOzbiBlc3RhYmxlY2lkYSBlbiBlbGxhLiBTaW4gZW1iYXJnbywgbG9zIGluZGl2aWR1b3MgbyBlbnRpZGFkZXMgcXVlIGhhbiByZWNpYmlkbyBPYnJhcyBEZXJpdmFkYXMgbyBDb2xlY3RpdmFzIGRlIFVzdGVkIGRlIGNvbmZvcm1pZGFkIGNvbiBlc3RhIExpY2VuY2lhLCBubyB2ZXLDoW4gdGVybWluYWRhcyBzdXMgbGljZW5jaWFzLCBzaWVtcHJlIHF1ZSBlc3RvcyBpbmRpdmlkdW9zIG8gZW50aWRhZGVzIHNpZ2FuIGN1bXBsaWVuZG8gw61udGVncmFtZW50ZSBsYXMgY29uZGljaW9uZXMgZGUgZXN0YXMgbGljZW5jaWFzLiBMYXMgU2VjY2lvbmVzIDEsIDIsIDUsIDYsIDcsIHkgOCBzdWJzaXN0aXLDoW4gYSBjdWFscXVpZXIgdGVybWluYWNpw7NuIGRlIGVzdGEgTGljZW5jaWEuCmIuIFN1amV0YSBhIGxhcyBjb25kaWNpb25lcyB5IHTDqXJtaW5vcyBhbnRlcmlvcmVzLCBsYSBsaWNlbmNpYSBvdG9yZ2FkYSBhcXXDrSBlcyBwZXJwZXR1YSAoZHVyYW50ZSBlbCBwZXLDrW9kbyBkZSB2aWdlbmNpYSBkZSBsb3MgZGVyZWNob3MgZGUgYXV0b3IgZGUgbGEgb2JyYSkuIE5vIG9ic3RhbnRlIGxvIGFudGVyaW9yLCBlbCBMaWNlbmNpYW50ZSBzZSByZXNlcnZhIGVsIGRlcmVjaG8gYSBwdWJsaWNhciB5L28gZXN0cmVuYXIgbGEgT2JyYSBiYWpvIGNvbmRpY2lvbmVzIGRlIGxpY2VuY2lhIGRpZmVyZW50ZXMgbyBhIGRlamFyIGRlIGRpc3RyaWJ1aXJsYSBlbiBsb3MgdMOpcm1pbm9zIGRlIGVzdGEgTGljZW5jaWEgZW4gY3VhbHF1aWVyIG1vbWVudG87IGVuIGVsIGVudGVuZGlkbywgc2luIGVtYmFyZ28sIHF1ZSBlc2EgZWxlY2Npw7NuIG5vIHNlcnZpcsOhIHBhcmEgcmV2b2NhciBlc3RhIGxpY2VuY2lhIG8gcXVlIGRlYmEgc2VyIG90b3JnYWRhICwgYmFqbyBsb3MgdMOpcm1pbm9zIGRlIGVzdGEgbGljZW5jaWEpLCB5IGVzdGEgbGljZW5jaWEgY29udGludWFyw6EgZW4gcGxlbm8gdmlnb3IgeSBlZmVjdG8gYSBtZW5vcyBxdWUgc2VhIHRlcm1pbmFkYSBjb21vIHNlIGV4cHJlc2EgYXRyw6FzLiBMYSBMaWNlbmNpYSByZXZvY2FkYSBjb250aW51YXLDoSBzaWVuZG8gcGxlbmFtZW50ZSB2aWdlbnRlIHkgZWZlY3RpdmEgc2kgbm8gc2UgbGUgZGEgdMOpcm1pbm8gZW4gbGFzIGNvbmRpY2lvbmVzIGluZGljYWRhcyBhbnRlcmlvcm1lbnRlLgogIAo4LiBWYXJpb3MuCmEuIENhZGEgdmV6IHF1ZSBVc3RlZCBkaXN0cmlidXlhIG8gcG9uZ2EgYSBkaXNwb3NpY2nDs24gcMO6YmxpY2EgbGEgT2JyYSBvIHVuYSBPYnJhIENvbGVjdGl2YSwgZWwgTGljZW5jaWFudGUgb2ZyZWNlcsOhIGFsIGRlc3RpbmF0YXJpbyB1bmEgbGljZW5jaWEgZW4gbG9zIG1pc21vcyB0w6lybWlub3MgeSBjb25kaWNpb25lcyBxdWUgbGEgbGljZW5jaWEgb3RvcmdhZGEgYSBVc3RlZCBiYWpvIGVzdGEgTGljZW5jaWEuCmIuIFNpIGFsZ3VuYSBkaXNwb3NpY2nDs24gZGUgZXN0YSBMaWNlbmNpYSByZXN1bHRhIGludmFsaWRhZGEgbyBubyBleGlnaWJsZSwgc2Vnw7puIGxhIGxlZ2lzbGFjacOzbiB2aWdlbnRlLCBlc3RvIG5vIGFmZWN0YXLDoSBuaSBsYSB2YWxpZGV6IG5pIGxhIGFwbGljYWJpbGlkYWQgZGVsIHJlc3RvIGRlIGNvbmRpY2lvbmVzIGRlIGVzdGEgTGljZW5jaWEgeSwgc2luIGFjY2nDs24gYWRpY2lvbmFsIHBvciBwYXJ0ZSBkZSBsb3Mgc3VqZXRvcyBkZSBlc3RlIGFjdWVyZG8sIGFxdcOpbGxhIHNlIGVudGVuZGVyw6EgcmVmb3JtYWRhIGxvIG3DrW5pbW8gbmVjZXNhcmlvIHBhcmEgaGFjZXIgcXVlIGRpY2hhIGRpc3Bvc2ljacOzbiBzZWEgdsOhbGlkYSB5IGV4aWdpYmxlLgpjLiBOaW5nw7puIHTDqXJtaW5vIG8gZGlzcG9zaWNpw7NuIGRlIGVzdGEgTGljZW5jaWEgc2UgZXN0aW1hcsOhIHJlbnVuY2lhZGEgeSBuaW5ndW5hIHZpb2xhY2nDs24gZGUgZWxsYSBzZXLDoSBjb25zZW50aWRhIGEgbWVub3MgcXVlIGVzYSByZW51bmNpYSBvIGNvbnNlbnRpbWllbnRvIHNlYSBvdG9yZ2FkbyBwb3IgZXNjcml0byB5IGZpcm1hZG8gcG9yIGxhIHBhcnRlIHF1ZSByZW51bmNpZSBvIGNvbnNpZW50YS4KZC4gRXN0YSBMaWNlbmNpYSByZWZsZWphIGVsIGFjdWVyZG8gcGxlbm8gZW50cmUgbGFzIHBhcnRlcyByZXNwZWN0byBhIGxhIE9icmEgYXF1w60gbGljZW5jaWFkYS4gTm8gaGF5IGFycmVnbG9zLCBhY3VlcmRvcyBvIGRlY2xhcmFjaW9uZXMgcmVzcGVjdG8gYSBsYSBPYnJhIHF1ZSBubyBlc3TDqW4gZXNwZWNpZmljYWRvcyBlbiBlc3RlIGRvY3VtZW50by4gRWwgTGljZW5jaWFudGUgbm8gc2UgdmVyw6EgbGltaXRhZG8gcG9yIG5pbmd1bmEgZGlzcG9zaWNpw7NuIGFkaWNpb25hbCBxdWUgcHVlZGEgc3VyZ2lyIGVuIGFsZ3VuYSBjb211bmljYWNpw7NuIGVtYW5hZGEgZGUgVXN0ZWQuIEVzdGEgTGljZW5jaWEgbm8gcHVlZGUgc2VyIG1vZGlmaWNhZGEgc2luIGVsIGNvbnNlbnRpbWllbnRvIG11dHVvIHBvciBlc2NyaXRvIGRlbCBMaWNlbmNpYW50ZSB5IFVzdGVkLgo=