Caracterización de la diversidad filogenética de circovirus porcino 2 procedente del estado de Paraná, Brasil
El Circovirus porcino 2 (PCV2) es uno de los patógenos con mayor importancia en el sector de producción porcina, ya que se asocia a diversas patologías que afectan a los cerdos domésticos a nivel mundial. Aunque en Brasil se ha implementado el uso de vacunas contra PCV2 la predominancia de los genot...
- Autores:
-
Guerra Jaramillo, Anyela Yiceth
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 0025
- Institución:
- Universidad de Córdoba
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- Repositorio Institucional Unicórdoba
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https://repositorio.unicordoba.edu.co/
- Palabra clave:
- Enfermedad sistémica por Circovirus porcino 2
ORF2
Análisi filogénetico
Coinfección
PCV2f
Systemic disease due to porcine circovirus 2
ORF2
Phylogenetic analysis
Coinfection
PCV2f
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- embargoedAccess
- License
- http://purl.org/coar/access_right/c_f1cf
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Caracterización de la diversidad filogenética de circovirus porcino 2 procedente del estado de Paraná, Brasil |
| title |
Caracterización de la diversidad filogenética de circovirus porcino 2 procedente del estado de Paraná, Brasil |
| spellingShingle |
Caracterización de la diversidad filogenética de circovirus porcino 2 procedente del estado de Paraná, Brasil Enfermedad sistémica por Circovirus porcino 2 ORF2 Análisi filogénetico Coinfección PCV2f Systemic disease due to porcine circovirus 2 ORF2 Phylogenetic analysis Coinfection PCV2f |
| title_short |
Caracterización de la diversidad filogenética de circovirus porcino 2 procedente del estado de Paraná, Brasil |
| title_full |
Caracterización de la diversidad filogenética de circovirus porcino 2 procedente del estado de Paraná, Brasil |
| title_fullStr |
Caracterización de la diversidad filogenética de circovirus porcino 2 procedente del estado de Paraná, Brasil |
| title_full_unstemmed |
Caracterización de la diversidad filogenética de circovirus porcino 2 procedente del estado de Paraná, Brasil |
| title_sort |
Caracterización de la diversidad filogenética de circovirus porcino 2 procedente del estado de Paraná, Brasil |
| dc.creator.fl_str_mv |
Guerra Jaramillo, Anyela Yiceth |
| dc.contributor.advisor.none.fl_str_mv |
Gastelbondo Pastrana, Bertha Irina |
| dc.contributor.author.none.fl_str_mv |
Guerra Jaramillo, Anyela Yiceth |
| dc.contributor.jury.none.fl_str_mv |
López Mejía, Yésica Paola Castro Cavadía, Carlos Javier |
| dc.subject.proposal.spa.fl_str_mv |
Enfermedad sistémica por Circovirus porcino 2 ORF2 Análisi filogénetico Coinfección PCV2f |
| topic |
Enfermedad sistémica por Circovirus porcino 2 ORF2 Análisi filogénetico Coinfección PCV2f Systemic disease due to porcine circovirus 2 ORF2 Phylogenetic analysis Coinfection PCV2f |
| dc.subject.keywords.eng.fl_str_mv |
Systemic disease due to porcine circovirus 2 ORF2 Phylogenetic analysis Coinfection PCV2f |
| description |
El Circovirus porcino 2 (PCV2) es uno de los patógenos con mayor importancia en el sector de producción porcina, ya que se asocia a diversas patologías que afectan a los cerdos domésticos a nivel mundial. Aunque en Brasil se ha implementado el uso de vacunas contra PCV2 la predominancia de los genotipos circulantes ha cambiado a lo largo de los años. Caracterizar la diversidad filogenética de Circovirus porcino tipo 2 procedente del estado de Paraná, Brasil. Se realizó un estudio experimental con 190 muestras de suero de cerdos crioconservadas en el IBTEC; fueron recolectados en el año 2020 en el estado de Paraná – Brasil, por la Agencia de Defensa Agropecuaria del Paraná. Se realizó detección molecular por RT-qPCR del fragmento ORF2 de Circovirus porcino 2, fue secuenciado mediante metodología Sanger. Las secuencias obtenidas fueron clasificadas filogenéticamente utilizando las herramientas bioinformáticas del software Geneious versión 2025.0. Se detectó la presencia de Circovirus porcino en el 15,3% de las muestras estudiadas. Se lograron obtener las secuencias del gen ORF2 de cuatro muestras; tres de ellas fueron identificadas como variante PCV2d, correspondiendo a la región oeste, centro occidental y norte central de Paraná, respectivamente. La variante PCV2d fue la secuencia de mayor prevalencia, y se obtuvo una secuencia de PCV2f procedente de la región sudoeste. PCV2d fue la variante de mayor prevalencia identificada en el estado de Paraná durante el año 2020. También se identificó la variante PCV2f, indicando la posibilidad de una mayor diversidad filogenética de Circovirus porcino 2 en esta zona. Se hace necesario realizar vigilancia y control epidemiológico de las variantes de PCV2 de forma continua para el monitoreo de su circulación. |
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0025 |
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0025-01-28 |
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2025-01-29T03:54:21Z |
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2025-01-29T03:54:21Z 2028-01-26 |
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info:eu-repo/semantics/bachelorThesis |
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Universidad de Córdoba |
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Repositorio Universidad de Córdoba |
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1. Correa-Fiz, F., Franzo, G., Llorens, A., Segalés, J., & Kekarainen, T. (2018). Porcine circovirus 2 (PCV-2) genetic variability under natural infection scenario reveals a complex network of viral quasispecies. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-33849-2 2. Li, D., Wang, J., Xu, S., Cai, S., Ao, C., Fang, L., Xiao, S., Chen, H., & Jiang, Y. (2017). Identification and functional analysis of the novel ORF6 protein of porcine circovirus type 2 in vitro. Veterinary Research Communications, 42(1), 1-10. https://doi.org/10.1007/s11259-017-9702-0 3. Franzo, G., Tucciarone, C. M., Cecchinato, M., & Drigo, M. (2016). Porcine circovirus type 2 (PCV2) evolution before and after the vaccination introduction: A large scale epidemiological study. Scientific Reports, 6(1). https://doi.org/10.1038/srep39458 4. Suh, J., Oh, T., & Chae, C. (2023b). Virulence comparison of 4 porcine circovirus type 2 (PCV-2) genotypes: 2a, 2b, 2d, and 2e with a single infection and co-infection with PCV-2 and porcine reproductive and respiratory syndrome virus (PRRSV). PubMed, 87(1), 41-50. https://pubmed.ncbi.nlm.nih.gov/36606036 5. In: CONGRESSO DA ABRAVES, 18., 2017, Goiânia. Suinocultura brasileira na era da tecnologia e da sustentabilidade: anais. Concórdia: Embrapa Suínos e Aves, 2017. v. 1. Palestras. p. 150-156. https://www.alice.cnptia.embrapa.br/alice/bitstream/doc/1081769/1/final8668.pdf 6. Choi, C., Choi, Y., Park, I., Lee, C., Kang, S., & Chun, T. (2018). The ORF5 protein of porcine circovirus type 2 enhances viral replication by dampening type I interferon expression in porcine epithelial cells. Veterinary Microbiology, 226, 50-58. https://doi.org/10.1016/j.vetmic.2018.10.005 7. Lv, Qz., Guo, Kk. & Zhang, Ym. Current understanding of genomic DNA of porcine circovirus type 2. Virus Genes 49, 1–10 (2014). https://doi.org/10.1007/s11262-014-1099-z 8. Kekarainen, T., Segalés, J. Porcine circovirus 2 immunology and viral evolution. Porc Health Manag 1, 17 (2015). https://doi.org/10.1186/s40813-015-0012-z 9. Palinski, R., Piñeyro, P., Shang, P., Yuan, F., Guo, R., Fang, Y., Byers, E., & Hause, B. M. (2017). A novel porcine Circovirus distantly related to known circoviruses is associated with porcine dermatitis and nephropathy syndrome and reproductive failure. Journal of Virology, 91(1). https://doi.org/10.1128/jvi.01879-16 10. Franzo, G., Cortey, M., Segalés, J., Hughes, J., & Drigo, M. (2016). Phylodynamic analysis of porcine circovirus type 2 reveals global waves of emerging genotypes and the circulation of recombinant forms. Molecular Phylogenetics And Evolution, 100, 269-280. https://doi.org/10.1016/j.ympev.2016.04.028 11. Associação Brasileira de Proteína Animal (ABPA). (2024). Relatório Anual 2024. https://abpa-br.org/wp-content/uploads/2024/04/ABPA-Relatorio-Anual-2024_capa_frango.pdf 12. Brasil: Paraná logra la mayor producción porcina en el primer semestre. (s. f.). https://www.3tres3.com/latam/ultima-hora/parana-logra-mayor-produccion-porcina-semestral_15795/#:~:text=De%20enero%20a%20junio%2C%20el,5%2C9%20millones%20de%20cabezas.&text=La%20encuesta%20del%20IBGE%20tambi%C3%A9n,de%202023%20/AEN%20/Brasil 13. Miotto, R., Pissetti, C., Bordin, L. C., & Zanella, J. R. C. (2024b). Genótipos de Circovírus Suíno Tipo 2 e PCV3 em Amostras Clínicas de Suínos no Brasil. Ciência Animal Brasileira, 25. https://doi.org/10.1590/1809-6891v25e-77826p 14. Kekarainen, T., Gonzalez, A., Llorens, A., & Segalés, J. (2014). Genetic variability of porcine circovirus 2 in vaccinating and non-vaccinating commercial farms. Journal Of General Virology, 95(8), 1734-1742. https://doi.org/10.1099/vir.0.065318-0 15. Zhao, Y., Cui, X., Sang, H., Wen, S., Han, L., Yang, P., Xiao, Y., & Hou, Y. (2024). The prevalence and genetic characteristics of porcine Circovirus type 2 in Shandong Province, China, 2018–2020. Current Issues in Molecular Biology, 46(12), 13542–13553. https://doi.org/10.3390/cimb46120809 16. Guo, J., Hou, L., Zhou, J., Wang, D., Cui, Y., Feng, X., & Liu, J. (2022). Porcine Circovirus type 2 vaccines: Commercial application and research advances. Viruses, 14(9), 2005. https://doi.org/10.3390/v14092005 17. Cnpsa, J. R. C. Z. (2017). Situação atual da circovirose no Brasil. http://www.alice.cnptia.embrapa.br/alice/handle/doc/1081769 18. Opriessnig, T., Karuppannan, A. K., de Castro, A. M. M. G., & Xiao, C. T. (2021). Circovirus porcinos: Estado actual, vacíos en el conocimiento y desafíos. Suis, (174), 22-25. https://www.ivis.org/sites/default/files/library/suis/174/Suis174_3.pdf 19. Wu, F., Xu, T., Lai, S.-Y., Ai, Y.-R., Zhou, Y.-C., Ge, L.-P., Sun, J., Liu, Z.-H., Zeng, X., Lang, L.-Q., Xu, Z.-W., & Zhu, L. (2024). Prevalence and genetic evolution analysis of porcine epidemic diarrhea virus and porcine circovirus type 2 in Sichuan Province, China, from 2023 to 2024. Frontiers in Veterinary Science, 11, 1475347. https://doi.org/10.3389/fvets.2024.1475347 20. da Silva, R., & Marnie Martins Gomes de Castro, A. (2022). Porcine circovirus 2: Status atual e seus desafios. PubVet, 16(04). https://doi.org/10.31533/pubvet.v16n04a1095.1-14 21. Bhattacharjee, U., Sen, A., & Sharma, I. (2021). A retrospective study reveals the Porcine circovirus-2f genotype predominant in the indigenous pig population of North-eastern India. Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases, 96(105100), 105100. https://doi.org/10.1016/j.meegid.2021.105100 22. Qi, X., Fang, Z., Meng, L., Xiang, X., Ju, Y., Cai, X., An, T., Sun, M., & Wang, H. (2024). The C3d-fused Porcine circovirus type 2d virus-like particle induced early and enhanced immune response and protected pigs against challenge. Veterinary Microbiology, 299(110305), 110305. https://doi.org/10.1016/j.vetmic.2024.110305 |
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Monterá, Cordoba, Colombia |
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Gastelbondo Pastrana, Bertha Irina97dba762-363e-4eb4-bac1-97a1394b2429-1Guerra Jaramillo, Anyela Yiceth308567f7-3f5d-490a-a975-21f00dda1ce8-1López Mejía, Yésica Paola22a0f47d-ff77-49a1-82f2-8cc4424561e8-1Castro Cavadía, Carlos Javierf1cab92d-3ee1-4449-8954-48691e8e7a08-12025-01-29T03:54:21Z2028-01-262025-01-29T03:54:21Z0025-01-28https://repositorio.unicordoba.edu.co/handle/ucordoba/8957Universidad de CórdobaRepositorio Universidad de Córdobahttps://repositorio.unicordoba.edu.co/El Circovirus porcino 2 (PCV2) es uno de los patógenos con mayor importancia en el sector de producción porcina, ya que se asocia a diversas patologías que afectan a los cerdos domésticos a nivel mundial. Aunque en Brasil se ha implementado el uso de vacunas contra PCV2 la predominancia de los genotipos circulantes ha cambiado a lo largo de los años. Caracterizar la diversidad filogenética de Circovirus porcino tipo 2 procedente del estado de Paraná, Brasil. Se realizó un estudio experimental con 190 muestras de suero de cerdos crioconservadas en el IBTEC; fueron recolectados en el año 2020 en el estado de Paraná – Brasil, por la Agencia de Defensa Agropecuaria del Paraná. Se realizó detección molecular por RT-qPCR del fragmento ORF2 de Circovirus porcino 2, fue secuenciado mediante metodología Sanger. Las secuencias obtenidas fueron clasificadas filogenéticamente utilizando las herramientas bioinformáticas del software Geneious versión 2025.0. Se detectó la presencia de Circovirus porcino en el 15,3% de las muestras estudiadas. Se lograron obtener las secuencias del gen ORF2 de cuatro muestras; tres de ellas fueron identificadas como variante PCV2d, correspondiendo a la región oeste, centro occidental y norte central de Paraná, respectivamente. La variante PCV2d fue la secuencia de mayor prevalencia, y se obtuvo una secuencia de PCV2f procedente de la región sudoeste. PCV2d fue la variante de mayor prevalencia identificada en el estado de Paraná durante el año 2020. También se identificó la variante PCV2f, indicando la posibilidad de una mayor diversidad filogenética de Circovirus porcino 2 en esta zona. Se hace necesario realizar vigilancia y control epidemiológico de las variantes de PCV2 de forma continua para el monitoreo de su circulación.Porcine Circovirus Type 2 (PCV2) is one of the most significant pathogens in the swine production sector, as it is associated with various pathologies affecting domestic pigs worldwide. Although vaccines against PCV2 have been implemented in Brazil, the prevalence of circulating genotypes has changed over the years. To characterize the phylogenetic diversity of Porcine Circovirus Type 2 from the state of Paraná, Brazil. An experimental study was conducted using 190 serum samples from cryopreserved pigs at IBTEC; these samples were collected in 2020 in the state of Paraná, Brazil, by the Paraná Agricultural Defense Agency. Molecular detection was performed by RT-qPCR targeting the ORF2 fragment of Porcine Circovirus Type 2, and sequencing was carried out using Sanger methodology. The obtained sequences were phylogenetically classified using the bioinformatics tools of Geneious software version 2025.0.The presence of Porcine Circovirus was detected in 15.3% of the samples studied. Sequences of the ORF2 gene were successfully obtained from four samples; three of them were identified as PCV2d variant, corresponding to the western, central-western, and northern-central regions of Paraná, respectively. The PCV2d variant was the most prevalent sequence, and one sequence of PCV2f was obtained from the southwestern region. PCV2d was the most prevalent variant identified in the state of Paraná in 2020. The PCV2f variant was also identified, suggesting a greater phylogenetic diversity of Porcine Circovirus Type 2 in this area. Continuous surveillance and epidemiological control of PCV2 variants are necessary for monitoring their circulation.PregradoBacteriólogo(a)Artículoapplication/pdfspaUniversidad de CórdobaFacultad de Ciencias de la SaludMonterá, Cordoba, ColombiaBacteriologíaCaracterización de la diversidad filogenética de circovirus porcino 2 procedente del estado de Paraná, BrasilTrabajo de grado - Pregradoinfo:eu-repo/semantics/bachelorThesishttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/acceptedVersionText1. Correa-Fiz, F., Franzo, G., Llorens, A., Segalés, J., & Kekarainen, T. (2018). Porcine circovirus 2 (PCV-2) genetic variability under natural infection scenario reveals a complex network of viral quasispecies. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-33849-22. Li, D., Wang, J., Xu, S., Cai, S., Ao, C., Fang, L., Xiao, S., Chen, H., & Jiang, Y. (2017). Identification and functional analysis of the novel ORF6 protein of porcine circovirus type 2 in vitro. Veterinary Research Communications, 42(1), 1-10. https://doi.org/10.1007/s11259-017-9702-03. Franzo, G., Tucciarone, C. M., Cecchinato, M., & Drigo, M. (2016). Porcine circovirus type 2 (PCV2) evolution before and after the vaccination introduction: A large scale epidemiological study. Scientific Reports, 6(1). https://doi.org/10.1038/srep394584. Suh, J., Oh, T., & Chae, C. (2023b). Virulence comparison of 4 porcine circovirus type 2 (PCV-2) genotypes: 2a, 2b, 2d, and 2e with a single infection and co-infection with PCV-2 and porcine reproductive and respiratory syndrome virus (PRRSV). PubMed, 87(1), 41-50. https://pubmed.ncbi.nlm.nih.gov/366060365. In: CONGRESSO DA ABRAVES, 18., 2017, Goiânia. Suinocultura brasileira na era da tecnologia e da sustentabilidade: anais. Concórdia: Embrapa Suínos e Aves, 2017. v. 1. Palestras. p. 150-156. https://www.alice.cnptia.embrapa.br/alice/bitstream/doc/1081769/1/final8668.pdf6. Choi, C., Choi, Y., Park, I., Lee, C., Kang, S., & Chun, T. (2018). The ORF5 protein of porcine circovirus type 2 enhances viral replication by dampening type I interferon expression in porcine epithelial cells. Veterinary Microbiology, 226, 50-58. https://doi.org/10.1016/j.vetmic.2018.10.0057. Lv, Qz., Guo, Kk. & Zhang, Ym. Current understanding of genomic DNA of porcine circovirus type 2. Virus Genes 49, 1–10 (2014). https://doi.org/10.1007/s11262-014-1099-z8. Kekarainen, T., Segalés, J. Porcine circovirus 2 immunology and viral evolution. Porc Health Manag 1, 17 (2015). https://doi.org/10.1186/s40813-015-0012-z9. Palinski, R., Piñeyro, P., Shang, P., Yuan, F., Guo, R., Fang, Y., Byers, E., & Hause, B. M. (2017). A novel porcine Circovirus distantly related to known circoviruses is associated with porcine dermatitis and nephropathy syndrome and reproductive failure. Journal of Virology, 91(1). https://doi.org/10.1128/jvi.01879-1610. Franzo, G., Cortey, M., Segalés, J., Hughes, J., & Drigo, M. (2016). Phylodynamic analysis of porcine circovirus type 2 reveals global waves of emerging genotypes and the circulation of recombinant forms. Molecular Phylogenetics And Evolution, 100, 269-280. https://doi.org/10.1016/j.ympev.2016.04.02811. Associação Brasileira de Proteína Animal (ABPA). (2024). Relatório Anual 2024. https://abpa-br.org/wp-content/uploads/2024/04/ABPA-Relatorio-Anual-2024_capa_frango.pdf12. Brasil: Paraná logra la mayor producción porcina en el primer semestre. (s. f.). https://www.3tres3.com/latam/ultima-hora/parana-logra-mayor-produccion-porcina-semestral_15795/#:~:text=De%20enero%20a%20junio%2C%20el,5%2C9%20millones%20de%20cabezas.&text=La%20encuesta%20del%20IBGE%20tambi%C3%A9n,de%202023%20/AEN%20/Brasil13. Miotto, R., Pissetti, C., Bordin, L. C., & Zanella, J. R. C. (2024b). Genótipos de Circovírus Suíno Tipo 2 e PCV3 em Amostras Clínicas de Suínos no Brasil. Ciência Animal Brasileira, 25. https://doi.org/10.1590/1809-6891v25e-77826p14. Kekarainen, T., Gonzalez, A., Llorens, A., & Segalés, J. (2014). Genetic variability of porcine circovirus 2 in vaccinating and non-vaccinating commercial farms. Journal Of General Virology, 95(8), 1734-1742. https://doi.org/10.1099/vir.0.065318-015. Zhao, Y., Cui, X., Sang, H., Wen, S., Han, L., Yang, P., Xiao, Y., & Hou, Y. (2024). The prevalence and genetic characteristics of porcine Circovirus type 2 in Shandong Province, China, 2018–2020. Current Issues in Molecular Biology, 46(12), 13542–13553. https://doi.org/10.3390/cimb4612080916. Guo, J., Hou, L., Zhou, J., Wang, D., Cui, Y., Feng, X., & Liu, J. (2022). Porcine Circovirus type 2 vaccines: Commercial application and research advances. Viruses, 14(9), 2005. https://doi.org/10.3390/v1409200517. Cnpsa, J. R. C. Z. (2017). Situação atual da circovirose no Brasil. http://www.alice.cnptia.embrapa.br/alice/handle/doc/108176918. Opriessnig, T., Karuppannan, A. K., de Castro, A. M. M. G., & Xiao, C. T. (2021). Circovirus porcinos: Estado actual, vacíos en el conocimiento y desafíos. Suis, (174), 22-25. https://www.ivis.org/sites/default/files/library/suis/174/Suis174_3.pdf19. Wu, F., Xu, T., Lai, S.-Y., Ai, Y.-R., Zhou, Y.-C., Ge, L.-P., Sun, J., Liu, Z.-H., Zeng, X., Lang, L.-Q., Xu, Z.-W., & Zhu, L. (2024). Prevalence and genetic evolution analysis of porcine epidemic diarrhea virus and porcine circovirus type 2 in Sichuan Province, China, from 2023 to 2024. Frontiers in Veterinary Science, 11, 1475347. https://doi.org/10.3389/fvets.2024.147534720. da Silva, R., & Marnie Martins Gomes de Castro, A. (2022). Porcine circovirus 2: Status atual e seus desafios. PubVet, 16(04). https://doi.org/10.31533/pubvet.v16n04a1095.1-1421. Bhattacharjee, U., Sen, A., & Sharma, I. (2021). A retrospective study reveals the Porcine circovirus-2f genotype predominant in the indigenous pig population of North-eastern India. Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases, 96(105100), 105100. https://doi.org/10.1016/j.meegid.2021.10510022. Qi, X., Fang, Z., Meng, L., Xiang, X., Ju, Y., Cai, X., An, T., Sun, M., & Wang, H. (2024). The C3d-fused Porcine circovirus type 2d virus-like particle induced early and enhanced immune response and protected pigs against challenge. 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