Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria

Cuando se hace referencia a la hepatitis viral del pato (HVP), se está hablando, de una infección de curso agudo que, además, es extremadamente contagiosa en patos cuyo tiempo de vida es de menos de 6 semanas de edad y, con frecuencia, en patos de menos de 3 semanas, esta suele estar clasificada en...

Full description

Autores:
Galindo Moreno, Tannia Marcela
Aragón Arboleda, Nicolás
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2021
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/34786
Acceso en línea:
https://hdl.handle.net/20.500.12494/34786
Palabra clave:
Hepatitis viral
Pato
Enfermedad
Infección
Migración
Colombia
TG 2021 MVZ 34786
Viral hepatitis
Duck
Disease
Infection
Migration
Colombia
Rights
openAccess
License
Atribución
id COOPER2_13f0d63c6c2d8e5efe5e79d8b8477aca
oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/34786
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria
title Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria
spellingShingle Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria
Hepatitis viral
Pato
Enfermedad
Infección
Migración
Colombia
TG 2021 MVZ 34786
Viral hepatitis
Duck
Disease
Infection
Migration
Colombia
title_short Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria
title_full Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria
title_fullStr Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria
title_full_unstemmed Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria
title_sort Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria
dc.creator.fl_str_mv Galindo Moreno, Tannia Marcela
Aragón Arboleda, Nicolás
dc.contributor.advisor.none.fl_str_mv Sanmiguel Plazas, Rosa Angélica
dc.contributor.author.none.fl_str_mv Galindo Moreno, Tannia Marcela
Aragón Arboleda, Nicolás
dc.subject.spa.fl_str_mv Hepatitis viral
Pato
Enfermedad
Infección
Migración
Colombia
topic Hepatitis viral
Pato
Enfermedad
Infección
Migración
Colombia
TG 2021 MVZ 34786
Viral hepatitis
Duck
Disease
Infection
Migration
Colombia
dc.subject.classification.spa.fl_str_mv TG 2021 MVZ 34786
dc.subject.other.spa.fl_str_mv Viral hepatitis
Duck
Disease
Infection
Migration
Colombia
description Cuando se hace referencia a la hepatitis viral del pato (HVP), se está hablando, de una infección de curso agudo que, además, es extremadamente contagiosa en patos cuyo tiempo de vida es de menos de 6 semanas de edad y, con frecuencia, en patos de menos de 3 semanas, esta suele estar clasificada en los tipos I, II y III. La HVP de tipo I puede desencadenarse por al menos tres genotipos distintos del virus de la hepatitis A del pato (VHPA), siendo estos un miembro del género Avihepatovirus, de la familia Picornaviridae. El más patógeno y diseminado es el VHPA de tipo I (VHPA-1), que en un principio se denominaba virus de la hepatitis del pato-1. Los virus VHPA-2 y VHPA-3 son dos genotipos del género Avihepatovirus que posteriormente han sido identificados como agentes etiológicos adicionales del VHP en los patos. Al ser observada como una enfermedad clínica, esta es caracterizada por un proceso de letargo y ataxia, seguidos de opistótonos y teniendo como desenlace la muerte del pato. Es probable, bajo otras circunstancias, que se presenten cuestiones como la esplenomegalia y tumefacción renal con cierta congestión de los vasos sanguíneos renales. Por otro lado, también se deben destacar todas aquellas lesiones microscópicas del hígado, que van desde la necrosis hepatocitaria extensa, hasta la hiperplasia del conducto biliar, junto con ciertos grados de variables de respuesta inflamatoria y hemorrágica. En Colombia, la enfermedad fue reportada por primera vez en 1984 en aves provenientes de la costa norte del país y fue declarada oficialmente ante la OIE en el año 2001. Ésta se reportó en lotes de pollos de engorde entre las 5 y 10 semanas de edad generando un cuadro clínico caracterizado por tener un curso rápido (24 horas o incluso menos) y una mortalidad acumulativa entre 3,7 y 6%, dando un tiempo limitado para actuar contra el virus. Es necesario realizar estudios que determinen la presencia de anticuerpos contra adenovirus tipo I y hepatitis con cuerpos de inclusión en granjas, con el objetivo de aportar al conocimiento del comportamiento de este agente etiológico que afecta las explotaciones avícolas del país. El presente trabajo pretende recopilar información actualizada al respecto de la hepatitis viral del pato y singular frecuencia de presentación en territorio Colombiano durante su ruta Migratoria.
publishDate 2021
dc.date.accessioned.none.fl_str_mv 2021-06-25T14:22:55Z
dc.date.available.none.fl_str_mv 2021-06-25T14:22:55Z
dc.date.issued.none.fl_str_mv 2021-06-24
dc.type.none.fl_str_mv Trabajo de grado - Pregrado
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/bachelorThesis
dc.type.version.none.fl_str_mv info:eu-repo/semantics/acceptedVersion
format http://purl.org/coar/resource_type/c_7a1f
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/34786
dc.identifier.bibliographicCitation.spa.fl_str_mv Galindo Moreno, T. M. y Aragón Arboleda, N. (2021). Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria. [tesis de pregrado, Universidad Cooperativa de Colombia]. Repositorio Institucional UCC. http://hdl.handle.net/20.500.12494/34786
url https://hdl.handle.net/20.500.12494/34786
identifier_str_mv Galindo Moreno, T. M. y Aragón Arboleda, N. (2021). Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria. [tesis de pregrado, Universidad Cooperativa de Colombia]. Repositorio Institucional UCC. http://hdl.handle.net/20.500.12494/34786
dc.relation.references.spa.fl_str_mv Guo WN, Zhu B, Ai L, Yang DL, Wang BJ. Animal models for the study of hepatitis B virus infection. Zool Res. 2018;39(1):25–31.
Chen ZY, Cheng AC, Wang MS, Xu DW, Zeng W, Li Z. Antiviral effects of PNA in duck hepatitis B virus infection model. Acta Pharmacol Sin. 2007;28(10):1652–8.
Zhang YY. Duck Hepatitis B Virus cccDNA amplification efficiency in natural infection is regulated by virus secretion efficiency. PLoS One [Internet]. 2015;10(12):1–15. Available from: http://dx.doi.org/10.1371/journal.pone.0145465
Sohn JA, Litwin S, Seeger C. Mechanism for CCC DNA Synthesis in Hepadnaviruses. PLoS One. 2009;4(11).
Ding XR, Yang J, Sun DC, Lou SK, Wang SQ. Whole genome expression profiling of hepatitis B virus-transfected cell line reveals the potential targets of anti-HBV drugs. Pharmacogenomics J. 2008;8(1):61–70.
Tang C, Lan D, Zhang H, Ma J, Yue H. Transcriptome Analysis of Duck Liver and Identification of Differentially Expressed Transcripts in Response to Duck Hepatitis A Virus Genotype C Infection. PLoS One. 2013;8(7):1–10.
Sun D, Wang M, Wen X, Cheng A, Jia R, Sun K, et al. Cleavage of poly(A)-binding protein by duck hepatitis A virus 3C protease. Sci Rep [Internet]. 2017;7(1):1–12. Available from: http://dx.doi.org/10.1038/s41598-017-16484-1
Yan L, Qu S, Liu G, Liu L, Yu Y, Ding G, et al. Comparative transcriptomic analysis of primary duck hepatocytes provides insight into differential susceptibility to DHBV infection. PLoS One [Internet]. 2016;11(2):1–20. Available from: http://dx.doi.org/10.1371/journal.pone.0149702
Li Q, Jia R, Liu S, Wang M, Zhu D, Chen S, et al. Complete genome sequence of the novel duck hepatitis B virus strain SCP01 from Sichuan Cherry Valley duck. Springerplus. 2016;5(1).
Chen X, Chen Y, Liu C, Li X, Liu H, Yin X, et al. Improved one-tube RT-PCR method for simultaneous detection and genotyping of duck hepatitis A virus subtypes 1 and 3. PLoS One [Internet]. 2019;14(8):1–14. Available from: http://dx.doi.org/10.1371/journal.pone.0219750
Wu X, Li X, Zhang Q, Wulin S, Bai X, Zhang T, et al. Identification of a conserved B-cell epitope on duck hepatitis a type 1 virus VP1 proteine0118041. PLoS One [Internet]. 2015;10(2):1–12. Available from: http://dx.doi.org/10.1371/journal.pone.0118041
Ludgate L, Adams C, Hu J. Phosphorylation State-Dependent interactions of hepadnavirus core protein with host factors. PLoS One. 2011;6(12).
Abdul F, Ndeboko B, Buronfosse T, Zoulim F, Kann M, Nielsen PE, et al. Potent Inhibition of Late Stages of Hepadnavirus Replication by a Modified Cell Penetrating Peptide. PLoS One. 2012;7(11).
Du H, Zhang S, Song M, Wang Y, Zeng L, Chen Y, et al. Assessment of a flavone-polysaccharide based prescription for treating duck virus hepatitis. PLoS One [Internet]. 2016;11(1):1–17. Available from: http://dx.doi.org/10.1371/journal.pone.0146046
Jia YY, Guan RF, Wu YH, Yu XP, Lin WY, Zhang YY, et al. Taraxacum mongolicum extract exhibits a protective effect on hepatocytes and an antiviral effect against hepatitis B virus in animal and human cells. Mol Med Rep. 2014;9(4):1381–7.
Zhao GW, Huang T, Wu D, Zhang L, Luo Z, Liu J, et al. Diagnosis and characterization of duck beak atrophy and dwarfism syndrome in chongqing of china. Vet Res Forum. 2019;10(2):169–72.
Zheng Q, Bai L, Zheng S, Liu M, Zhang J, Wang T, et al. Efficient inhibition of duck hepatitis B virus DNA by the CRISPR/Cas9 system. Mol Med Rep. 2017;16(5):7199–204.
Köck J, Rösler C, Zhang JJ, Blum HE, Nassal M, Thoma C. Generation of covalently closed circular DNA of hepatitis B viruses via intracellular recycling is regulated in a virus specific manner. PLoS Pathog. 2010;6(9).
Nassal M. HBV cccDNA: Viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015;64(12):1972–84.
Liu X, Kong X. Isolation, identification and attenuation of a pathogenic duck hepatitis virus type 1 in China, and complete genomic sequence comparison between the embryo-passaged, attenuated derivatives and their parent strain. Pol J Vet Sci. 2019;22(1):163–71.
Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005;5(3):215–29.
Liu K, Luckenbaugh L, Ning X, Xi J, Hu J. Multiple roles of core protein linker in hepatitis B virus replication. PLoS Pathog [Internet]. 2018;14(5):1–26. Available from: http://dx.doi.org/10.1371/journal.ppat.1007085
Noordeen F, Scougall CA, Grosse A, Qiao Q, Ajilian BB, Reaiche-Miller G, et al. Therapeutic antiviral effect of the nucleic acid polymer REP 2055 against persistent duck hepatitis B virus infection. PLoS One [Internet]. 2015;10(11):1–21. Available from: http://dx.doi.org/10.1371/journal.pone.0140909
Zhao Y, Ben H, Qu S, Zhou X, Yan L, Xu B, et al. Proteomic analysis of primary duck hepatocytes infected with duck hepatitis B virus. Proteome Sci. 2010;8.
van Hemert FJ, van de Klundert MAA, Lukashov V V., Kootstra NA, Berkhout B, Zaaijer HL. Protein X of hepatitis B virus: Origin and structure similarity with the central domain of DNA glycosylase. PLoS One. 2011;6(8).
Petersen J, Dandri M, Mier W, Lütgehetmann M, Volz T, Von Weizsäcker F, et al. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nat Biotechnol. 2008;26(3):335–41.
Urban S, Schwarz C, Marx UC, Zentgraf H, Schaller H, Multhaup G. Receptor recognition by a hepatitis B virus reveals a novel mode of high affinity virus-receptor interaction. EMBO J. 2000;19(6):1217–27.
Lai Y, Zeng N, Wang M, Cheng A, Yang Q, Wu Y, et al. The VP3 protein of duck hepatitis A virus mediates host cell adsorption and apoptosis. Sci Rep [Internet]. 2019;9(1):1–13. Available from: http://dx.doi.org/10.1038/s41598-019-53285-0
Ou X, Mao S, Cao J, Cheng A, Wang M, Zhu D, et al. Comparative analysis of virus-host interactions caused by a virulent and an attenuated duck hepatitis A virus genotype 1. PLoS One [Internet]. 2017;12(6). Available from: http://dx.doi.org/10.1371/journal.pone.0178993
Gómez MM, Hernández LL, Luz M, Ortiz P. Poxvirus, Herpervirus, Adenovirus, Papovavirus y Hepadnavirus. 2007;1(2):288–97.
Xu Q, Chen Y, Zhao WM, Huang ZY, Zhang Y, Li X, et al. DNA methylation and regulation of the CD8A after duck hepatitis virus type 1 infection. PLoS One. 2014;9(2):1–8.
Kim MC, Kim MJ, Kwon YK, Lindberg AM, Joh SJ, Kwon HM, et al. Development of duck hepatitis A virus type 3 vaccine and its use to protect ducklings against infections. Vaccine. 2009;27(48):6688–94.
Seitz S, Urban S, Antoni C, Böttcher B. Cryo-electron microscopy of hepatitis B virions reveals variability in envelope capsid interactions. EMBO J. 2007;26(18):4160–7.
Paran N, Geiger B, Shaul Y. HBV infection of cell culture: Evidence for multivalent and cooperative attachment. EMBO J. 2001;20(16):4443–53.
Wu F, Lu F, Fan X, Chao J, Liu C, Pan Q, et al. Immune-related miRNA-mRNA regulation network in the livers of DHAV-3-infected ducklings. BMC Genomics. 2020;21(1):1–15.
Guo F, Zhao Q, Sheraz M, Cheng J, Qi Y, Su Q, et al. HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways. PLoS Pathog [Internet]. 2017;13(9):1–25. Available from: http://dx.doi.org/10.1371/journal.ppat.1006658
Shih C, Wu SY, Chou SF, Yuan TTT. Virion Secretion of Hepatitis B Virus Naturally Occurring Core Antigen Variants. Cells. 2020;10(1).
Kitamura K, Wang Z, Chowdhury S, Simadu M, Koura M, Muramatsu M. Uracil DNA Glycosylase Counteracts APOBEC3G-Induced Hypermutation of Hepatitis B Viral Genomes: Excision Repair of Covalently Closed Circular DNA. PLoS Pathog. 2013;9(5).
Bashir S, Paeshuyse J. Construction of Antibody Phage Libraries and Their Application in Veterinary Immunovirology. Antibodies. 2020;9(2):21.
Ma X, Sheng Z, Huang B, Qi L, Li Y, Yu K, et al. Molecular evolution and genetic analysis of the major capsid protein VP1 of duck hepatitis a viruses: Implications for antigenic stability. PLoS One [Internet]. 2015;10(7):1–14. Available from: http://dx.doi.org/10.1371/journal.pone.0132982
Robaczewska M, Guerret S, Remy JS, Chemin I, Offensperger WB, Chevallier M, et al. Inhibition of hepadnaviral replication by polyethylenimine-based intravenous delivery of antisense phosphodiester oligodeoxynucleotides to the liver. Gene Ther. 2001;8(11):874–81.
Landmann M, Scheibner D, Graaf A, Gischke M, Koethe S, Fatola OI, et al. A Semiquantitative Scoring System for Histopathological and Immunohistochemical Assessment of Lesions and Tissue Tropism in Avian Influenza. Viruses. 2021;13(5):868.
Wetzel D, Chan JA, Suckow M, Barbian A, Weniger M, Jenzelewski V, et al. Display of malaria transmission-blocking antigens on chimeric duck hepatitis B virus-derived virus-like particles produced in Hansenula polymorpha. PLoS One [Internet]. 2019;14(9):1–23. Available from: http://dx.doi.org/10.1371/journal.pone.0221394
Köck J, Rösler C, Zhang J, Blum HE, Nassal M, Thoma C. Human hepatitis B virus production in avian cells is characterized by enhanced RNA splicing and the presence of capsids containing shortened genomes. PLoS One. 2012;7(5).
Seeger C, Mason WS. Sodium-dependent taurocholic cotransporting polypeptide: A candidate receptor for human hepatitis B virus. Gut. 2013;62(8):1093–5.
Tsai WL, Chung RT. Viral hepatocarcinogenesis. Oncogene [Internet]. 2010;29(16):2309–24. Available from: http://dx.doi.org/10.1038/onc.2010.36
Luo J, Xi J, Gao L, Hu J. Role of hepatitis B virus capsid phosphorylation in nucleocapsid disassembly and covalently closed circular DNA formation [Internet]. Vol. 16, PLoS Pathogens. 2020. 1–31 p. Available from: http://dx.doi.org/10.1371/journal.ppat.1008459
Guillot C, Martel N, Berby F, Bordes I, Hantz O, Blanchet M, et al. Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes. PLoS One. 2017;12(6):1–15.
Dallmeier K, Schultz U, Nassal M. Heterologous replacement of the supposed host determining region of avihepadnaviruses: High in vivo infectivity despite low infectivity for hepatocytes. PLoS Pathog. 2008;4(12).
Du H, Yang J, Bai J, Ming K, Shi J, Yao F, et al. A flavone-polysaccharide based prescription attenuates the mitochondrial dysfunction induced by duck hepatitis A virus type 1. PLoS One [Internet]. 2017;12(4):1–15. Available from: http://dx.doi.org/10.1371/journal.pone.0175495
(OIE, ORGANIZACIÓN MUNDIAL DE SANIDAD ANIMAL, 2018), Hepatitis Viral del Pato. Recuperado el 23 de junio de 2021 de https://www.oie.int/es/enfermedad/hepatitis-viral-del-pato/.
dc.rights.license.none.fl_str_mv Atribución
dc.rights.accessrights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv Atribución
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 34 p.
dc.publisher.spa.fl_str_mv Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina Veterinaría y Zootecnia, Ibagué
dc.publisher.program.spa.fl_str_mv Medicina veterinaria y zootecnia
dc.publisher.place.spa.fl_str_mv Ibagué
institution Universidad Cooperativa de Colombia
bitstream.url.fl_str_mv https://repository.ucc.edu.co/bitstreams/1754524d-9e2a-4940-9f61-000005e7db7d/download
https://repository.ucc.edu.co/bitstreams/8f74296c-ac0d-40c9-8986-aea4caf87bff/download
https://repository.ucc.edu.co/bitstreams/fe1be33e-07a5-423d-a1cb-b64634ee3c3d/download
https://repository.ucc.edu.co/bitstreams/48092fd6-bd73-47c6-af96-9f131aac41f3/download
https://repository.ucc.edu.co/bitstreams/febeffc1-a076-474b-bb5d-f6691ae94a98/download
https://repository.ucc.edu.co/bitstreams/a3c692d1-86c3-4c66-8783-0073e381ad52/download
https://repository.ucc.edu.co/bitstreams/98ed7461-e93b-47d8-ab7f-78a3eda6d7a9/download
bitstream.checksum.fl_str_mv 9b40563bed3b8de24e9b2c1a7c38555a
9d93835c49def145e1d518675ab13633
3bce4f7ab09dfc588f126e1e36e98a45
c8c7fe58dd6ec3deb1f100cd114a6c8b
16f5f4a743aeadb1efe96879efec5b44
ceb80cf93d906b5fec225e3e483d04da
a495a3373a515269f30b6767336ff9a6
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad Cooperativa de Colombia
repository.mail.fl_str_mv bdigital@metabiblioteca.com
_version_ 1808788992630456320
spelling Sanmiguel Plazas, Rosa AngélicaGalindo Moreno, Tannia MarcelaAragón Arboleda, Nicolás2021-06-25T14:22:55Z2021-06-25T14:22:55Z2021-06-24https://hdl.handle.net/20.500.12494/34786Galindo Moreno, T. M. y Aragón Arboleda, N. (2021). Hepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoria. [tesis de pregrado, Universidad Cooperativa de Colombia]. Repositorio Institucional UCC. http://hdl.handle.net/20.500.12494/34786Cuando se hace referencia a la hepatitis viral del pato (HVP), se está hablando, de una infección de curso agudo que, además, es extremadamente contagiosa en patos cuyo tiempo de vida es de menos de 6 semanas de edad y, con frecuencia, en patos de menos de 3 semanas, esta suele estar clasificada en los tipos I, II y III. La HVP de tipo I puede desencadenarse por al menos tres genotipos distintos del virus de la hepatitis A del pato (VHPA), siendo estos un miembro del género Avihepatovirus, de la familia Picornaviridae. El más patógeno y diseminado es el VHPA de tipo I (VHPA-1), que en un principio se denominaba virus de la hepatitis del pato-1. Los virus VHPA-2 y VHPA-3 son dos genotipos del género Avihepatovirus que posteriormente han sido identificados como agentes etiológicos adicionales del VHP en los patos. Al ser observada como una enfermedad clínica, esta es caracterizada por un proceso de letargo y ataxia, seguidos de opistótonos y teniendo como desenlace la muerte del pato. Es probable, bajo otras circunstancias, que se presenten cuestiones como la esplenomegalia y tumefacción renal con cierta congestión de los vasos sanguíneos renales. Por otro lado, también se deben destacar todas aquellas lesiones microscópicas del hígado, que van desde la necrosis hepatocitaria extensa, hasta la hiperplasia del conducto biliar, junto con ciertos grados de variables de respuesta inflamatoria y hemorrágica. En Colombia, la enfermedad fue reportada por primera vez en 1984 en aves provenientes de la costa norte del país y fue declarada oficialmente ante la OIE en el año 2001. Ésta se reportó en lotes de pollos de engorde entre las 5 y 10 semanas de edad generando un cuadro clínico caracterizado por tener un curso rápido (24 horas o incluso menos) y una mortalidad acumulativa entre 3,7 y 6%, dando un tiempo limitado para actuar contra el virus. Es necesario realizar estudios que determinen la presencia de anticuerpos contra adenovirus tipo I y hepatitis con cuerpos de inclusión en granjas, con el objetivo de aportar al conocimiento del comportamiento de este agente etiológico que afecta las explotaciones avícolas del país. El presente trabajo pretende recopilar información actualizada al respecto de la hepatitis viral del pato y singular frecuencia de presentación en territorio Colombiano durante su ruta Migratoria.Duck virus hepatitis (DVH) is an acute course infection that is also extremely contagious in ducks less than 6 weeks of age and often in ducks less than 3 weeks of age and is usually classified into types I, II and III. Type I DVH can be triggered by at least three different genotypes of duck hepatitis A virus (DHAV), being a member of the genus Avihepatovirus, family Picornaviridae. The most pathogenic and widespread is the type I HPAV (HPAV-1), which was originally called duck hepatitis virus-1. VHPA-2 and VHPA-3 are two genotypes of the genus Avihepatovirus that have subsequently been identified as additional aetiological agents of VHP in ducks. When observed as a clinical disease, it is characterised by a process of lethargy and ataxia, followed by opisthotonos and leading to death of the duck. Under other circumstances, issues such as splenomegaly and renal swelling with some congestion of the renal blood vessels are likely to occur. On the other hand, microscopic lesions of the liver, ranging from extensive hepatocyte necrosis to bile duct hyperplasia, along with varying degrees of inflammatory response and haemorrhage, should also be noted. In Colombia, the disease was first reported in 1984 in birds from the northern coast of the country and was officially declared to the OIE in 2001. It was reported in broiler flocks between 5 and 10 weeks of age, generating a clinical picture characterised by a rapid course (24 hours or even less) and a cumulative mortality between 3.7 and 6%, giving a limited time to act against the virus. So far, there are no reports on the prevalence of the disease in Colombia. Based on the above, it is necessary to carry out studies to determine the presence of antibodies against adenovirus type I and hepatitis with inclusion bodies in farms, with the aim of contributing to the knowledge of the behaviour of this aetiological agent that affects poultry farms in the country. It is also important to promote research in the departments of Cundinamarca and Santander, where there is a high concentration of commercial poultry, in order to promote the control and prevention of the virus to avoid diseases of economic impact on the Colombian poultry industry. The objective aims to compile updated information on viral hepatitis in ducks and its singular frequency of presentation in Colombian territory during its migratory route.tannia.galindom@campusucc.edu.conicolas.aragona@campusucc.edu.co34 p.Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina Veterinaría y Zootecnia, IbaguéMedicina veterinaria y zootecniaIbaguéHepatitis viralPatoEnfermedadInfecciónMigraciónColombiaTG 2021 MVZ 34786Viral hepatitisDuckDiseaseInfectionMigrationColombiaHepatitis viral del pato y su presentación en el ánade real o azulón (ánade platyrhynchos), en el territorio colombiano durante su ruta migratoriaTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/acceptedVersionAtribucióninfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Guo WN, Zhu B, Ai L, Yang DL, Wang BJ. Animal models for the study of hepatitis B virus infection. Zool Res. 2018;39(1):25–31.Chen ZY, Cheng AC, Wang MS, Xu DW, Zeng W, Li Z. Antiviral effects of PNA in duck hepatitis B virus infection model. Acta Pharmacol Sin. 2007;28(10):1652–8.Zhang YY. Duck Hepatitis B Virus cccDNA amplification efficiency in natural infection is regulated by virus secretion efficiency. PLoS One [Internet]. 2015;10(12):1–15. Available from: http://dx.doi.org/10.1371/journal.pone.0145465Sohn JA, Litwin S, Seeger C. Mechanism for CCC DNA Synthesis in Hepadnaviruses. PLoS One. 2009;4(11).Ding XR, Yang J, Sun DC, Lou SK, Wang SQ. Whole genome expression profiling of hepatitis B virus-transfected cell line reveals the potential targets of anti-HBV drugs. Pharmacogenomics J. 2008;8(1):61–70.Tang C, Lan D, Zhang H, Ma J, Yue H. Transcriptome Analysis of Duck Liver and Identification of Differentially Expressed Transcripts in Response to Duck Hepatitis A Virus Genotype C Infection. PLoS One. 2013;8(7):1–10.Sun D, Wang M, Wen X, Cheng A, Jia R, Sun K, et al. Cleavage of poly(A)-binding protein by duck hepatitis A virus 3C protease. Sci Rep [Internet]. 2017;7(1):1–12. Available from: http://dx.doi.org/10.1038/s41598-017-16484-1Yan L, Qu S, Liu G, Liu L, Yu Y, Ding G, et al. Comparative transcriptomic analysis of primary duck hepatocytes provides insight into differential susceptibility to DHBV infection. PLoS One [Internet]. 2016;11(2):1–20. Available from: http://dx.doi.org/10.1371/journal.pone.0149702Li Q, Jia R, Liu S, Wang M, Zhu D, Chen S, et al. Complete genome sequence of the novel duck hepatitis B virus strain SCP01 from Sichuan Cherry Valley duck. Springerplus. 2016;5(1).Chen X, Chen Y, Liu C, Li X, Liu H, Yin X, et al. Improved one-tube RT-PCR method for simultaneous detection and genotyping of duck hepatitis A virus subtypes 1 and 3. PLoS One [Internet]. 2019;14(8):1–14. Available from: http://dx.doi.org/10.1371/journal.pone.0219750Wu X, Li X, Zhang Q, Wulin S, Bai X, Zhang T, et al. Identification of a conserved B-cell epitope on duck hepatitis a type 1 virus VP1 proteine0118041. PLoS One [Internet]. 2015;10(2):1–12. Available from: http://dx.doi.org/10.1371/journal.pone.0118041Ludgate L, Adams C, Hu J. Phosphorylation State-Dependent interactions of hepadnavirus core protein with host factors. PLoS One. 2011;6(12).Abdul F, Ndeboko B, Buronfosse T, Zoulim F, Kann M, Nielsen PE, et al. Potent Inhibition of Late Stages of Hepadnavirus Replication by a Modified Cell Penetrating Peptide. PLoS One. 2012;7(11).Du H, Zhang S, Song M, Wang Y, Zeng L, Chen Y, et al. Assessment of a flavone-polysaccharide based prescription for treating duck virus hepatitis. PLoS One [Internet]. 2016;11(1):1–17. Available from: http://dx.doi.org/10.1371/journal.pone.0146046Jia YY, Guan RF, Wu YH, Yu XP, Lin WY, Zhang YY, et al. Taraxacum mongolicum extract exhibits a protective effect on hepatocytes and an antiviral effect against hepatitis B virus in animal and human cells. Mol Med Rep. 2014;9(4):1381–7.Zhao GW, Huang T, Wu D, Zhang L, Luo Z, Liu J, et al. Diagnosis and characterization of duck beak atrophy and dwarfism syndrome in chongqing of china. Vet Res Forum. 2019;10(2):169–72.Zheng Q, Bai L, Zheng S, Liu M, Zhang J, Wang T, et al. Efficient inhibition of duck hepatitis B virus DNA by the CRISPR/Cas9 system. Mol Med Rep. 2017;16(5):7199–204.Köck J, Rösler C, Zhang JJ, Blum HE, Nassal M, Thoma C. Generation of covalently closed circular DNA of hepatitis B viruses via intracellular recycling is regulated in a virus specific manner. PLoS Pathog. 2010;6(9).Nassal M. HBV cccDNA: Viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015;64(12):1972–84.Liu X, Kong X. Isolation, identification and attenuation of a pathogenic duck hepatitis virus type 1 in China, and complete genomic sequence comparison between the embryo-passaged, attenuated derivatives and their parent strain. Pol J Vet Sci. 2019;22(1):163–71.Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005;5(3):215–29.Liu K, Luckenbaugh L, Ning X, Xi J, Hu J. Multiple roles of core protein linker in hepatitis B virus replication. PLoS Pathog [Internet]. 2018;14(5):1–26. Available from: http://dx.doi.org/10.1371/journal.ppat.1007085Noordeen F, Scougall CA, Grosse A, Qiao Q, Ajilian BB, Reaiche-Miller G, et al. Therapeutic antiviral effect of the nucleic acid polymer REP 2055 against persistent duck hepatitis B virus infection. PLoS One [Internet]. 2015;10(11):1–21. Available from: http://dx.doi.org/10.1371/journal.pone.0140909Zhao Y, Ben H, Qu S, Zhou X, Yan L, Xu B, et al. Proteomic analysis of primary duck hepatocytes infected with duck hepatitis B virus. Proteome Sci. 2010;8.van Hemert FJ, van de Klundert MAA, Lukashov V V., Kootstra NA, Berkhout B, Zaaijer HL. Protein X of hepatitis B virus: Origin and structure similarity with the central domain of DNA glycosylase. PLoS One. 2011;6(8).Petersen J, Dandri M, Mier W, Lütgehetmann M, Volz T, Von Weizsäcker F, et al. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nat Biotechnol. 2008;26(3):335–41.Urban S, Schwarz C, Marx UC, Zentgraf H, Schaller H, Multhaup G. Receptor recognition by a hepatitis B virus reveals a novel mode of high affinity virus-receptor interaction. EMBO J. 2000;19(6):1217–27.Lai Y, Zeng N, Wang M, Cheng A, Yang Q, Wu Y, et al. The VP3 protein of duck hepatitis A virus mediates host cell adsorption and apoptosis. Sci Rep [Internet]. 2019;9(1):1–13. Available from: http://dx.doi.org/10.1038/s41598-019-53285-0Ou X, Mao S, Cao J, Cheng A, Wang M, Zhu D, et al. Comparative analysis of virus-host interactions caused by a virulent and an attenuated duck hepatitis A virus genotype 1. PLoS One [Internet]. 2017;12(6). Available from: http://dx.doi.org/10.1371/journal.pone.0178993Gómez MM, Hernández LL, Luz M, Ortiz P. Poxvirus, Herpervirus, Adenovirus, Papovavirus y Hepadnavirus. 2007;1(2):288–97.Xu Q, Chen Y, Zhao WM, Huang ZY, Zhang Y, Li X, et al. DNA methylation and regulation of the CD8A after duck hepatitis virus type 1 infection. PLoS One. 2014;9(2):1–8.Kim MC, Kim MJ, Kwon YK, Lindberg AM, Joh SJ, Kwon HM, et al. Development of duck hepatitis A virus type 3 vaccine and its use to protect ducklings against infections. Vaccine. 2009;27(48):6688–94.Seitz S, Urban S, Antoni C, Böttcher B. Cryo-electron microscopy of hepatitis B virions reveals variability in envelope capsid interactions. EMBO J. 2007;26(18):4160–7.Paran N, Geiger B, Shaul Y. HBV infection of cell culture: Evidence for multivalent and cooperative attachment. EMBO J. 2001;20(16):4443–53.Wu F, Lu F, Fan X, Chao J, Liu C, Pan Q, et al. Immune-related miRNA-mRNA regulation network in the livers of DHAV-3-infected ducklings. BMC Genomics. 2020;21(1):1–15.Guo F, Zhao Q, Sheraz M, Cheng J, Qi Y, Su Q, et al. HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways. PLoS Pathog [Internet]. 2017;13(9):1–25. Available from: http://dx.doi.org/10.1371/journal.ppat.1006658Shih C, Wu SY, Chou SF, Yuan TTT. Virion Secretion of Hepatitis B Virus Naturally Occurring Core Antigen Variants. Cells. 2020;10(1).Kitamura K, Wang Z, Chowdhury S, Simadu M, Koura M, Muramatsu M. Uracil DNA Glycosylase Counteracts APOBEC3G-Induced Hypermutation of Hepatitis B Viral Genomes: Excision Repair of Covalently Closed Circular DNA. PLoS Pathog. 2013;9(5).Bashir S, Paeshuyse J. Construction of Antibody Phage Libraries and Their Application in Veterinary Immunovirology. Antibodies. 2020;9(2):21.Ma X, Sheng Z, Huang B, Qi L, Li Y, Yu K, et al. Molecular evolution and genetic analysis of the major capsid protein VP1 of duck hepatitis a viruses: Implications for antigenic stability. PLoS One [Internet]. 2015;10(7):1–14. Available from: http://dx.doi.org/10.1371/journal.pone.0132982Robaczewska M, Guerret S, Remy JS, Chemin I, Offensperger WB, Chevallier M, et al. Inhibition of hepadnaviral replication by polyethylenimine-based intravenous delivery of antisense phosphodiester oligodeoxynucleotides to the liver. Gene Ther. 2001;8(11):874–81.Landmann M, Scheibner D, Graaf A, Gischke M, Koethe S, Fatola OI, et al. A Semiquantitative Scoring System for Histopathological and Immunohistochemical Assessment of Lesions and Tissue Tropism in Avian Influenza. Viruses. 2021;13(5):868.Wetzel D, Chan JA, Suckow M, Barbian A, Weniger M, Jenzelewski V, et al. Display of malaria transmission-blocking antigens on chimeric duck hepatitis B virus-derived virus-like particles produced in Hansenula polymorpha. PLoS One [Internet]. 2019;14(9):1–23. Available from: http://dx.doi.org/10.1371/journal.pone.0221394Köck J, Rösler C, Zhang J, Blum HE, Nassal M, Thoma C. Human hepatitis B virus production in avian cells is characterized by enhanced RNA splicing and the presence of capsids containing shortened genomes. PLoS One. 2012;7(5).Seeger C, Mason WS. Sodium-dependent taurocholic cotransporting polypeptide: A candidate receptor for human hepatitis B virus. Gut. 2013;62(8):1093–5.Tsai WL, Chung RT. Viral hepatocarcinogenesis. Oncogene [Internet]. 2010;29(16):2309–24. Available from: http://dx.doi.org/10.1038/onc.2010.36Luo J, Xi J, Gao L, Hu J. Role of hepatitis B virus capsid phosphorylation in nucleocapsid disassembly and covalently closed circular DNA formation [Internet]. Vol. 16, PLoS Pathogens. 2020. 1–31 p. Available from: http://dx.doi.org/10.1371/journal.ppat.1008459Guillot C, Martel N, Berby F, Bordes I, Hantz O, Blanchet M, et al. Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes. PLoS One. 2017;12(6):1–15.Dallmeier K, Schultz U, Nassal M. Heterologous replacement of the supposed host determining region of avihepadnaviruses: High in vivo infectivity despite low infectivity for hepatocytes. PLoS Pathog. 2008;4(12).Du H, Yang J, Bai J, Ming K, Shi J, Yao F, et al. A flavone-polysaccharide based prescription attenuates the mitochondrial dysfunction induced by duck hepatitis A virus type 1. PLoS One [Internet]. 2017;12(4):1–15. Available from: http://dx.doi.org/10.1371/journal.pone.0175495(OIE, ORGANIZACIÓN MUNDIAL DE SANIDAD ANIMAL, 2018), Hepatitis Viral del Pato. Recuperado el 23 de junio de 2021 de https://www.oie.int/es/enfermedad/hepatitis-viral-del-pato/.PublicationORIGINAL2021_hepatitis_viral_pato.pdf2021_hepatitis_viral_pato.pdfapplication/pdf213510https://repository.ucc.edu.co/bitstreams/1754524d-9e2a-4940-9f61-000005e7db7d/download9b40563bed3b8de24e9b2c1a7c38555aMD512021_hepatitis_viral_pato-FormatoLicenciaUso.pdf2021_hepatitis_viral_pato-FormatoLicenciaUso.pdfapplication/pdf231812https://repository.ucc.edu.co/bitstreams/8f74296c-ac0d-40c9-8986-aea4caf87bff/download9d93835c49def145e1d518675ab13633MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-84334https://repository.ucc.edu.co/bitstreams/fe1be33e-07a5-423d-a1cb-b64634ee3c3d/download3bce4f7ab09dfc588f126e1e36e98a45MD53THUMBNAIL2021_hepatitis_viral_pato.pdf.jpg2021_hepatitis_viral_pato.pdf.jpgGenerated Thumbnailimage/jpeg3962https://repository.ucc.edu.co/bitstreams/48092fd6-bd73-47c6-af96-9f131aac41f3/downloadc8c7fe58dd6ec3deb1f100cd114a6c8bMD542021_hepatitis_viral_pato-FormatoLicenciaUso.pdf.jpg2021_hepatitis_viral_pato-FormatoLicenciaUso.pdf.jpgGenerated Thumbnailimage/jpeg5007https://repository.ucc.edu.co/bitstreams/febeffc1-a076-474b-bb5d-f6691ae94a98/download16f5f4a743aeadb1efe96879efec5b44MD55TEXT2021_hepatitis_viral_pato.pdf.txt2021_hepatitis_viral_pato.pdf.txtExtracted texttext/plain56645https://repository.ucc.edu.co/bitstreams/a3c692d1-86c3-4c66-8783-0073e381ad52/downloadceb80cf93d906b5fec225e3e483d04daMD562021_hepatitis_viral_pato-FormatoLicenciaUso.pdf.txt2021_hepatitis_viral_pato-FormatoLicenciaUso.pdf.txtExtracted texttext/plain5973https://repository.ucc.edu.co/bitstreams/98ed7461-e93b-47d8-ab7f-78a3eda6d7a9/downloada495a3373a515269f30b6767336ff9a6MD5720.500.12494/34786oai:repository.ucc.edu.co:20.500.12494/347862024-08-09 12:44:40.413open.accesshttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.comVU5JVkVSU0lEQUQgQ09PUEVSQVRJVkEgREUgQ09MT01CSUEKUkVQT1NJVE9SSU9TIElOU1RJVFVDSU9OQUxFUwpMSUNFTkNJQSBERSBVU08KClBvciBtZWRpbyBkZWwgcHJlc2VudGUgZG9jdW1lbnRvLCBlbCBBdXRvcihlcyksIG1heW9yIChlcykgZGUgZWRhZCwgcXVpZW4gZW4gYWRlbGFudGUgc2UgZGVub21pbmFyw6EgZWwgQVVUT1IsIGNvbmZpZXJlIGEgbGEgVU5JVkVSU0lEQUQgQ09PUEVSQVRJVkEgREUgQ09MT01CSUEsIGNvbiBOSVQuIDg2MC0wMjk5MjQtNywgdW5hIExJQ0VOQ0lBIERFIFVTTyBkZSBvYnJhLCBiYWpvIGxhcyBzaWd1aWVudGVzIGNvbmRpY2lvbmVzLgoKQ0zDgVVTVUxBUwoKUFJJTUVSQS4gT2JqZXRvLiBFTCBBVVRPUiBwb3IgZXN0ZSBhY3RvIGF1dG9yaXphIGxhIHV0aWxpemFjacOzbiBkZSBsYSBvYnJhLCBkZSBjb25mb3JtaWRhZCBjb24gbG8gZXN0aXB1bGFkbyBhIGNvbnRpbnVhY2nDs246IAoKKGEpIFBhcmEgZWZlY3RvcyBkZSBsYSBwcmVzZW50ZSBsaWNlbmNpYSBzZSBhdXRvcml6YSBsYSByZXByb2R1Y2Npw7NuIGRlIGxhIG9icmEgYW50ZXJpb3JtZW50ZSBjaXRhZGEsIGxhIGN1YWwgc2UgYWxvamFyw6EgZW4gZm9ybWF0byBkaWdpdGFsIGVuIGxhcyBwbGF0YWZvcm1hcyBvIHJlcG9zaXRvcmlvcyBhZG1pbmlzdHJhZG9zIHBvciBsYSBVTklWRVJTSURBRCBvIGVuIG90cm8gdGlwbyBkZSByZXBvc2l0b3Jpb3MgZXh0ZXJub3MgbyBww6FnaW5hcyB3ZWIgZXNjb2dpZG9zIHBvciBsYSBVTklWRVJTSURBRCwgcGFyYSBmaW5lcyBkZSBkaWZ1c2nDs24geSBkaXZ1bGdhY2nDs24uIEFkaWNpb25hbG1lbnRlLCBzZSBhdXRvcml6YSBhIHF1ZSBsb3MgdXN1YXJpb3MgaW50ZXJub3MgeSBleHRlcm5vcyBkZSBkaWNoYXMgcGxhdGFmb3JtYXMgbyByZXBvc2l0b3Jpb3MgcmVwcm9kdXpjYW4gbyBkZXNjYXJndWVuIGxhIG9icmEsIHNpbiDDoW5pbW8gZGUgbHVjcm8sIHBhcmEgZmluZXMgcHJpdmFkb3MsIGVkdWNhdGl2b3MgbyBhY2Fkw6ltaWNvczsgc2llbXByZSB5IGN1YW5kbyBubyBzZSB2aW9sZW4gYWN1ZXJkb3MgY29uIGVkaXRvcmVzLCBwZXJpb2RvcyBkZSBlbWJhcmdvIG8gYWN1ZXJkb3MgZGUgY29uZmlkZW5jaWFsaWRhZCBxdWUgYXBsaXF1ZW4uCgooYikgU2UgYXV0b3JpemEgbGEgY29tdW5pY2FjacOzbiBww7pibGljYSB5IGxhIHB1ZXN0YSBhIGRpc3Bvc2ljacOzbiBkZSBsYSBvYnJhIG1lbmNpb25hZGEsIGVuIGFjY2VzbyBhYmllcnRvLCBwYXJhIHN1IHV0aWxpemFjacOzbiBlbiBsYXMgcGxhdGFmb3JtYXMgbyByZXBvc2l0b3Jpb3MgYWRtaW5pc3RyYWRvcyBwb3IgbGEgVU5JVkVSU0lEQUQuCgooYykgTG8gYW50ZXJpb3IgZXN0YXLDoSBzdWpldG8gYSBsYXMgZGVmaW5pY2lvbmVzIGNvbnRlbmlkYXMgZW4gbGEgRGVjaXNpw7NuIEFuZGluYSAzNTEgZGUgMTk5MyB5IGxhIExleSAyMyBkZSAxOTgyLgoKClNFR1VOREEuIE9yaWdpbmFsaWRhZCB5IHJlY2xhbWFjaW9uZXMuIEVsIEFVVE9SIGRlY2xhcmEgcXVlIGxhIE9CUkEgZXMgb3JpZ2luYWwgeSBxdWUgZXMgZGUgc3UgY3JlYWNpw7NuIGV4Y2x1c2l2YSwgbm8gZXhpc3RpZW5kbyBpbXBlZGltZW50byBkZSBjdWFscXVpZXIgbmF0dXJhbGV6YSAoZW1iYXJnb3MsIHVzbyBkZSBtYXRlcmlhbCBwcm90ZWdpZG8gcG9yIGRlcmVjaG9zIGRlIGF1dG9yKSBwYXJhIGxhIGNvbmNlc2nDs24gZGUgbG9zIGRlcmVjaG9zIHByZXZpc3RvcyBlbiBlc3RlIGFjdWVyZG8uIEVsIEFVVE9SIHJlc3BvbmRlcsOhIHBvciBjdWFscXVpZXIgYWNjacOzbiBkZSByZWl2aW5kaWNhY2nDs24sIHBsYWdpbyB1IG90cmEgY2xhc2UgZGUgcmVjbGFtYWNpw7NuIHF1ZSBhbCByZXNwZWN0byBwdWRpZXJhIHNvYnJldmVuaXIuCgpURVJDRVJBLiBDb250cmFwcmVzdGFjacOzbi4gRWwgQVVUT1IgYXV0b3JpemEgYSBxdWUgc3Ugb2JyYSBzZWEgdXRpbGl6YWRhIGRlIGNvbmZvcm1pZGFkIGNvbiBsYSBjbMOhdXN1bGEgUFJJTUVSQSBkZSBmb3JtYSBncmF0dWl0YSwgZXMgZGVjaXIsIHF1ZSBsYSB1dGlsaXphY2nDs24gZGUgbGEgbWlzbWEgbm8gZ2VuZXJhIG5pbmfDum4gcGFnbyBvIHJlZ2Fsw61hcyBlbiBmYXZvciBkZSBlc3RlLgoKQ1VBUlRBLiBUaXR1bGFyaWRhZCBkZSBkZXJlY2hvcy4gRWwgcHJlc2VudGUgY29udHJhdG8gbm8gdHJhbnNmaWVyZSBsYSB0aXR1bGFyaWRhZCBkZSBsb3MgZGVyZWNob3MgcGF0cmltb25pYWxlcyBzb2JyZSBsYXMgb2JyYXMgYW50ZXJpb3JtZW50ZSBtZW5jaW9uYWRhcyBhIGxhIFVOSVZFUlNJREFELiDDmm5pY2FtZW50ZSBoYWNlIHJlbGFjacOzbiBhIHVuYSBsaWNlbmNpYSBubyBleGNsdXNpdmEgZW4gbG9zIHTDqXJtaW5vcyB5IGNvbmRpY2lvbmVzIGFudGVyaW9ybWVudGUgcGFjdGFkb3MuCgpRVUlOVEEuIENyw6lkaXRvcy4gTGEgVU5JVkVSU0lEQUQgc2UgY29tcHJvbWV0ZSBhIGRhciBhbCBBVVRPUiwgZWwgcmVjb25vY2ltaWVudG8gZGVudHJvIGNhZGEgZm9ybWEgZGUgdXRpbGl6YWNpw7NuIGVuIGxhIG9icmEuIExvcyBjcsOpZGl0b3MgZGViZW4gZmlndXJhciBlbiBjYWRhIHVubyBkZSBsb3MgZm9ybWF0b3MgbyByZWdpc3Ryb3MgZGUgcHVibGljYWNpw7NuLiBObyBjb25zdGl0dWlyw6EgdW5hIHZpb2xhY2nDs24gYSBsb3MgZGVyZWNob3MgbW9yYWxlcyBkZWwgYXV0b3IgbGEgbm8gcmVwcm9kdWNjacOzbiwgY29tdW5pY2FjacOzbiBvIGRlbcOhcyB1dGlsaXphY2lvbmVzIGRlIGxhIG9icmEuIExhIHV0aWxpemFjacOzbiBvIG5vIGRlIGxhIG9icmEsIGFzw60gY29tbyBzdSBmb3JtYSBkZSB1dGlsaXphY2nDs24gc2Vyw6EgZmFjdWx0YWQgZXhjbHVzaXZhIGRlIGxhIFVOSVZFUlNJREFELgogClNFWFRBLiBEdXJhY2nDs24geSB0ZXJyaXRvcmlvLiBMYSBwcmVzZW50ZSBsaWNlbmNpYSBkZSB1c28gcXVlIHNlIG90b3JnYSBhIGZhdm9yIGRlIGxhIFVOSVZFUlNJREFEIHRlbmRyw6EgdW5hIGR1cmFjacOzbiBlcXVpdmFsZW50ZSBhbCB0w6lybWlubyBkZSBwcm90ZWNjacOzbiBsZWdhbCBkZSBsYSBvYnJhIHkgcGFyYSB0b2RvcyBsb3MgcGHDrXNlcyBkZWwgbXVuZG8uCgpTw4lQVElNQS4gVXNvIGRlIENyZWF0aXZlIENvbW1vbnMuIEVsIEFVVE9SIGF1dG9yaXphcsOhIGxhIGRpZnVzacOzbiBkZSBzdSBjb250ZW5pZG8gYmFqbyB1bmEgbGljZW5jaWEgQ3JlYXRpdmUgQ29tbW9ucyBhdHJpYnVjacOzbiA0LjAgaW50ZXJuYWNpb25hbCwgcXVlIGRlYmVyw6EgaW5jbHVpcnNlIGVuIGVsIGNvbnRlbmlkby4gCgpPQ1RBVkEuIERlcmVjaG8gZGUgZXhjbHVzacOzbi4gQ2FkYSBhdXRvciBwdWVkZSBpbmRpY2FyIGVuIGVsIG1vbWVudG8gZGUgZGVww7NzaXRvIGRlbCBjb250ZW5pZG8gcXVlIGVsIHRleHRvIGNvbXBsZXRvIGRlIGxhIHByb2R1Y2Npw7NuIGFjYWTDqW1pY2EgbyBjaWVudMOtZmljYSBubyBlc3RlIGNvbiBhY2Nlc28gYWJpZXJ0byBlbiBlbCBSZXBvc2l0b3JpbyBJbnN0aXR1Y2lvbmFsIHBvciBtb3Rpdm9zIGRlIGNvbmZpZGVuY2lhbGlkYWQsIHBvcnF1ZSBzZSBlbmN1ZW50cmUgZW4gdsOtYXMgZGUgb2J0ZW5lciB1biBkZXJlY2hvIGRlIHByb3BpZWRhZCBpbmR1c3RyaWFsIG8gZXhpc3RpciBhY3VlcmRvcyBwcmV2aW9zIGNvbiB0ZXJjZXJvcyAoZWRpdG9yaWFsZXMsIHJldmlzdGFzIGNpZW50w61maWNhcywgb3RyYXMgaW5zdGl0dWNpb25lcykuIEVsIGF1dG9yIHNlIGNvbXByb21ldGUgYSBkZXBvc2l0YXIgbG9zIG1ldGFkYXRvcyBlIGluZm9ybWFyIGVsIHRpZW1wbyBkZSBlbWJhcmdvIGR1cmFudGUgZWwgY3VhbCBlbCB0ZXh0byBjb21wbGV0byB0ZW5kcsOhIGFjY2VzbyByZXN0cmluZ2lkby4gCgpOT1ZFTkEuIEVsIEFVVE9SIGFsIGFjZXB0YXIgZXN0YSBsaWNlbmNpYSBhZHVjZSBxdWUgZXN0YSBwcm9kdWNjacOzbiBzZSBkZXNhcnJvbGzDsyBlbiBlbCBwZXJpb2RvIGVuIHF1ZSBzZSBlbmN1ZW50cmEgY29uIHbDrW5jdWxvcyBjb24gTGEgVW5pdmVyc2lkYWQuCgpEw4lDSU1BLiBOb3JtYXMgYXBsaWNhYmxlcy4gUGFyYSBsYSBpbnRlcnByZXRhY2nDs24geSBjdW1wbGltaWVudG8gZGVsIHByZXNlbnRlIGFjdWVyZG8gbGFzIHBhcnRlcyBzZSBzb21ldGVuIGEgbGEgRGVjaXNpw7NuIEFuZGluYSAzNTEgZGUgMTk5MywgbGEgTGV5IDIzIGRlIDE5ODIgeSBkZW3DoXMgbm9ybWFzIGFwbGljYWJsZXMgZGUgQ29sb21iaWEuIEFkZW3DoXMsIGEgbGFzIG5vcm1hcyBJbnN0aXR1Y2lvbmFsZXMgcXVlIGFwbGlxdWVuLgoKTGEgcHJlc2VudGUgbGljZW5jaWEgc2UgYXV0b3JpemEgZW4gbGEgZmVjaGEgZGUgcHVibGljYWNpw7NuIGVuIGxvcyByZXBvc2l0b3Jpb3MgaW5zdGl0dWNpb25hbGVzLgo=