Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica
Incluye figuras.
- Autores:
-
Salgado Ruíz, Jefersson Stiven
Jaramillo-Hernández, Dumar Alexander
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2021
- Institución:
- Universidad de los Llanos
- Repositorio:
- Repositorio Digital Universidad de los LLanos
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unillanos.edu.co:001/3124
- Acceso en línea:
- https://repositorio.unillanos.edu.co/handle/001/3124
https://repositorio.unillanos.edu.co/
- Palabra clave:
- Peste porcina
Enfermedad transmisible
Inmunología
Estrés oxidativo
Piroptosis
Communicable diseases
Immunology
Oxidative stress
Pyroptosis
- Rights
- openAccess
- License
- Derechos Reservados - Universidad de Los Llanos, 2021
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Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica |
| title |
Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica |
| spellingShingle |
Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica Peste porcina Enfermedad transmisible Inmunología Estrés oxidativo Piroptosis Communicable diseases Immunology Oxidative stress Pyroptosis |
| title_short |
Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica |
| title_full |
Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica |
| title_fullStr |
Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica |
| title_full_unstemmed |
Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica |
| title_sort |
Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica |
| dc.creator.fl_str_mv |
Salgado Ruíz, Jefersson Stiven Jaramillo-Hernández, Dumar Alexander |
| dc.contributor.author.none.fl_str_mv |
Salgado Ruíz, Jefersson Stiven Jaramillo-Hernández, Dumar Alexander |
| dc.subject.armarc.none.fl_str_mv |
Peste porcina |
| topic |
Peste porcina Enfermedad transmisible Inmunología Estrés oxidativo Piroptosis Communicable diseases Immunology Oxidative stress Pyroptosis |
| dc.subject.proposal.spa.fl_str_mv |
Enfermedad transmisible Inmunología Estrés oxidativo Piroptosis |
| dc.subject.proposal.eng.fl_str_mv |
Communicable diseases Immunology Oxidative stress Pyroptosis |
| description |
Incluye figuras. |
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2021 |
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2021 |
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2023-11-08T13:56:51Z |
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2023-11-08T13:56:51Z |
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Salgado-Ruíz, J. S. y Jaramillo-Hernández, D. A. (2021). Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica. Revista MVZ Córdoba,27(1). |
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2361 |
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Universidad de los Llanos |
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Repositorio Universidad de los Llanos |
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Salgado-Ruíz, J. S. y Jaramillo-Hernández, D. A. (2021). Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica. Revista MVZ Córdoba,27(1). 0122-0268 2361 Universidad de los Llanos Repositorio Universidad de los Llanos |
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https://repositorio.unillanos.edu.co/handle/001/3124 https://repositorio.unillanos.edu.co/ |
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Kleiboeker SB. Swine fever: classical swine fever and African swine fever. Vet Clin North Am Food Anim Pract. 2002; 18(3):431451.https://doi.org/10.1016/S07490720(02)00028-2 Smith DB, Meyers G, Bukh J, Gould EA, Monath T, Scott Muerhoff A, et al. Proposed revision to the taxonomy of the genus Pestivirus, family Flaviviridae. J Gen Virol. 2017; 98(8):2106-2112. https://doi. org/10.1099/jgv.0.000873 Elbers AR, Vos JH, Bouma A, van Exsel AC , Stegeman A. Assessment of the use of gross lesions at post-mortem to detect outbreaks of classical swine fever. Vet Microbiol. 2003;96(4):345-356. https://doi.org/10.1016/j.vetmic.2003.09.005 Gong W, Jia J, Zhang B, Mi S, Zhang L, Xie X, et al. Serum metabolomic profiling of piglets infected with virulent classical swine fever virus. Front Microbiol. 2017; 8:731.https://doi.org/10.3389/fmicb.2017.00731 Feng L, Li XQ, Li XN, Li J, Meng X, Zhang H, et al. In vitro infection with classical swine fever virus inhibits the transcription of immune response genes. Virology J. 2012; 9(1):1-11. https://doi.org/10.1186/1743422X-9-175 OIE. World organisation for animal health. Clasical swine fever. Technical.Disease Cards; 2020. https://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/Disease_cards/CLASSICAL_SWINE_FEVER.pdf Sun J, Shi Z, Guo H, Tu C. Changes in the porcine peripheral blood mononuclear cell proteome induced by infection with highly virulent classical swine fever virus. J Gen Virol. 2010; 91(9):2254–2262. https://doi. org/10.1099/vir.0.022020-0 Meyers G, Rümenapf T, Thiel HJ. Molecular cloning and nucleotide sequence of the genome of hog cholera virus. Virology. 1989; 171(2):555-567. https://doi.org/10.1016/0042-6822(89)90625-9 Paton D, McGoldrick A, Greiser-Wilke I, Parchariyanon S, Song J, Liou PP, Belak S. Genetic typing of classical swine fever virus. Vet Microbiol. 2000; 73(2-3):137157. https://doi.org/10.1016/S03781135(00)00141-3 Rios L, Núñez JI, Díaz de Arce H, Ganges L, Pérez L. Revisiting the genetic diversity of classical swine fever virus: A proposal for new genotyping and subgenotyping schemes of classification. Transbound Emerg Dis. 2018; 65(4):963-971. https://doi. org/10.1111/tbed.12909 Beer M, Goller K, Staubach C, Blome S. Genetic variability and distribution of Classical swine fever virus. Anim Health Res Rev. 2015; 16(1):33. https://doi.org/10.1017/ S1466252315000109 Sabogal Z, Mogollón J, Rincón M, Clavijo A. Phylogenetic analysis of recent isolates of classical swine fever virus from Colombia. Virus Res. 2006; 115(1):99-103. https://doi.org/10.1016/j.virusres.2005.06.016 Pereda A, Greiser Wilke I, Schmitt B, Rincon M, Mogollon JD, Sabogal Z, et al. Phylogenetic analysis of classical swine fever virus (CSFV) field isolates from outbreaks in South and Central America. Virus Res. 2005; 110(1-2):111-118. https://doi. org/10.1016/j.virusres.2005.01.011 Silva MN, Silva D, Leite AS, Gomes AL, Freitas AC, Pinheiro-Junior J, Jesus AL. Identification and genetic characterization of classical swine fever virus isolates in Brazil: a new subgenotype. Arch Virol. 2017;162(3):817-822. https://doi.org/10.1007/ s00705-016-3145-8 Gong W, Wu J, Lu Z, Zhang L, Qin S, Chen F, et al. Genetic diversity of subgenotype 2.1 isolates of classical swine fever virus. Infect Genet Evol. 2016; 41:218-226. https://doi.org/10.1016/j.meegid.2016.04.002 An D, Lim S, Choe S, Kim K, Cha R, Cho I, et al. Evolutionary dynamics of classical swine fever virus in South Korea:1987–2017. Vet Microbiol. 2018; 225:79-88. https://doi.org/10.1016/j.vetmic.2018.09.0209/12 Depner K, Müller A, Gruber A, Rodriguez A, Bickhardt K, Liess B. Classical swine fever in wild boar (Sus scrofa) experimental infections and viral persistence. DTW. Dtsch Tierarztl Wochenschr. 1995; 102(10):381-384. https://pubmed.ncbi.nlm.nih.gov/8591736/24. Schulz K, Staubach C, Blome S. African and classical swine fever: similarities, differences and epidemiological consequences. Vet. Res. 2017; 48(1):1-13. https://doi.org/10.1186/s13567-017-0490-x Weesendorp E, Stegeman A, Loeffen WL. Quantification of classical swine fever virus in aerosols originating from pigs infected with strains of high, moderate or low virulence. Vet Microbiol. 2009; 135(34):222-230. https://doi.org/10.1016/j. vetmic.2008.09.073 Bøtner A, Belsham G.Virus survival in slurry: analysis of the stability of foot-and-mouth disease, classical swine fever, bovine viral diarrhoea and swine influenza viruses. Vet Microbiol. 2012; 157(1-2):41-49. https://doi.org/10.1016/j.vetmic.2011.12.010 Stoian A , Petrovan V, Constance L, Olcha M, Dee S, Diel D, et al. Stability of classical swine fever virus and pseudorabies virus in animal feed ingredients exposed to transpacific shipping conditions. Transbound Emerg Dis. 2020; 67(4):1623-1632. https://doi.org/10.1111/tbed.13498 Cabezón O, Colom Cadena A, Muñoz González S, Pérez Simó M, Bohórquez J, Rosell R, et al. Postnatal Persistent Infection With Classical Swine Fever Virus in Wild Boar: ¿A Strategy for Viral Maintenance? Transbound Emerg Dis. 2017; 64(2):651655. https://doi.org/10.1111/tbed.1239 Bohorquez J, Muñoz González S, Pérez Simó M, Revilla C, Domínguez J, Ganges L. Identification of an immunosuppressive cell population during classical swine fever virus infection and its role in viral persistence in the host. Viruses. 2019; 11(9):822. https://doi.org/10.3390/v11090822 Bohórquez J, Wang M, Pérez Simó M, Vidal E, Rosell R, Ganges L. Low CD4/CD8 ratio in classical swine fever postnatal persistent infection generated at 3 weeks after birth. Transbound Emerg Dis. 2019; 66(2):752762. https://doi.org/10.1111/tbed.13080 Rios L, Coronado L, Naranjo D, Martínez O, Perera C, Hernandez L, et al. Deciphering the emergence, genetic diversity and evolution of classical swine fever virus. Sci Rep. 2017; 7(1):1-18. https://doi.org/10.1038/s41598-017-18196-y ICA. Programa de Erradicación Peste Porcina Clásica. Instituto Colombiano Agropecuario: Colombia; 2018. ttps://www.ica.gov. co/getdoc/ea9c6aa0-a5fc-472f-869b975b27d7ac35/peste-porcina-clasica-(1).aspx Pineda P, Deluque A, Peña M, Diaz O, Allepuz A, Casal J. Descriptive epidemiology of classical swine fever outbreaks in the period 2013-2018 in Colombia. PloS One. 2020; 15(6):e0234490. https://doi.org/10.1371/ journal.pone.0234490 Katz DR. Recent developments in immunopathology. Second Edition. in Encyclopedia of Immunology Delves PJ, Roitt IM. Academic Press; 1998. https://doi.org/10.1006/rwei.1999.0342 Dräger C, Beer M, Blome S. Porcine complement regulatory protein CD46 and heparan sulfates are the major factors for classical swine fever virus attachment in vitro. Arch Virol. 2015; 160(3):739-746. https://doi.org/10.1007/s00705-0142313-y Zhang Y, Liu Y, Xiao F, Liu C, Liang X, Chen J, et al. Rab5, Rab7, and Rab11 are required for caveola-dependent endocytosis of classical swine fever virus in porcine alveolar macrophages. J Virol. 2018; 92(15):e0079718. https://doi.org/10.1128/JVI.00797-18 Shi B, Liu C, Zhou J, Wang S, Gao Z, Zhang X, et al. Entry of classical swine fever virus into PK-15 cells via a pH-, dynamin, and cholesterol-dependent, clathrin-mediated endocytic pathway that requires Rab5 and Rab7. J Virol. 2016; 90(20):9194-9208. https://doi.org/10.1128/JVI.00688-16 Zheng G, Li L, Zhang Y, Qu L, Wang W, Li M, et al. MERTK is a host factor that promotes classical swine fever virus entry and antagonizes innate immune response in PK-15 cells. Emerg Microbes Infect. 2020; 9(1):571-581. https://doi.org/10.1080/22 221751.2020.1738278 Liu C, Liu Y, Cheng Y, Zhang Y, Zhang J, Liang X, et al. The ESCRT-I Subunit Tsg101 Plays Novel Dual Roles in Entry and Replication of Classical Swine Fever Virus. J Virol. 2021; 95(6):e01928-20. https://doi.org/10.1128/ JVI.01928-20 Yuan F, Li D, Li C, Zhang Y, Song H, Li S, et al. ADAM17 is an essential attachment factor for classical swine fever virus. PLoS Pathog. 2021; 17(3):e1009393. https://doi. org/10.1371/journal.ppat.1009393 Kataria AK, Kataria N. Evaluation of oxidative stress in pigs affected with classical swine fever. Porcine Res. 2012; 2(2):35-38. http://www.porc.bioflux.com.ro/docs/2012.35-38.pdf He L, Zhang Y, Fang Y, Liang W, Lin J, Cheng M. Classical swine fever virus induces oxidative stress in swine umbilical vein endothelial cells. BMC Vet Res. 2012; 10(1):1-9. https://doi.org/10.1186/s12917-014-0279-3 Li S, Wang J, He WR, Feng S, Li Y, Wang X, et al. Thioredoxin 2 is a novel E2-interacting protein that inhibits the replication of classical swine fever virus. J Virol. 2015; 89:8510-8524. https://doi.org/10.1128/ JVI.00429-15 Zaffuto K, Piccone M, Burrage T, Balinsky C, Risatti G, Borca M, et al Classical swine fever virus inhibits nitric oxide production in infected macrophages. J Gen Virol.2007; 88(11):3007-3012. https://doi.org/10.1099/vir.0.83042-0 Cao Z, Yang Q, Zheng M, Lv H, Kang K, Zhang Y. Classical swine fever virus nonstructural proteins modulate Toll-like receptor signaling pathways in porcine monocyte-derived macrophages. Vet Microbiol. 2019; 230:101-109. https://doi. org/10.1016/j.vetmic.2019.01.025 Chen L, Dong X, Zhao M, Shen H, Wang J, Pei J, et al. Classical swine fever virus failed to activate nuclear factor-kappa b signaling pathway both in vitro and in vivo. Virol J. 2012; 9(1):1-8. https://doi.org/10.1186/1743-422X-9-293 Dong X, Tang S. Classical swine fever virus NS5A protein changed inflammatory cytokine secretion in porcine alveolar macrophages by inhibiting the NF-κB signaling pathway. Virol J. 2016; 13(1):19. https://doi.org/10.1186/s12985-0160545-z Tizard IR. Introducción a la inmunología veterinaria, octava edición. capitulo sexto; señalización celular: las citoquinas y sus receptores; ruta de transducción de señales: La ruta de JAK-STAT. ELSEVIER; 2009. Wang J, Chen S, Liao Y, Zhang E, Feng S, Yu S, et al. Mitogen-activated protein kinase 2, a novel E2-interacting protein, promotes the growth of classical swine fever virus via attenuation of the JAK-STAT signaling pathway. J Virol. 2016; 90(22):10271-10283. https://doi.org/10.1128/JVI.01407-16 Bensaude E, Turner JL, Wakeley PR, Sweetman DA, Pardieu C, Drew TW, et al. Classical swine fever virus induces proinflammatory cytokines and tissue factor expression and inhibits apoptosis and interferon synthesis during the establishment of long-term infection of porcine vascular endothelial cells. J Gen Virol.2004; 85(4):1029-1037. https://doi. org/10.1099/vir.0.19637-0 Jinghan W, Yuan S, Meng X-Yu, Lian-Feng L, Yongfeng L, Yuzi L,Wenjing W, et al. Comprehensive evaluation of the host responses to infection with differentially virulent classical swine fever virus strains in pigs. Virus Res. 2018; 255:68-76. https://doi.org/10.1016/j.virusres.2018.06.012 Lin Z, Liang W, Kang K, Li H, Cao Z, Zhang Y. Classical swine fever virus and p7 protein induce secretion of IL-1β in macrophages. J Gen Virol. 2014; 95(12):2693-269. https://doi.org/10.1099/vir.0.068502-0 Fan S, Yuan J, Deng S, Chen Y, Xie B, Wu K, et al. Activation of Interleukin-1_ Release by the Classical Swine Fever Virus Is Dependent on the NLRP3 Inflammasome, Which Affects Virus Growth in Monocytes. Front. Cell Infect Microbiol. 2018; 8:225. https://doi.org/10.3389/fcimb.2018.00225 Carrasco CP, Rigden RC, Vincent IE, Balmelli C, Ceppi M, Bauhofer, O, et al. Interaction of classical swine fever virus with dendritic cells. J Gen Virol. 2004; 85(6):1633-1641. https://doi.org/10.1099/vir.0.19716-0 Westermann B. Bioenergetic role of mitochondrial fusion and fission. Biochim Biophys Acta. 2012; 1817(10):18331838. https://doi.org/10.1016/j.bbabio.2012.02.033 Zorov DB, Vorobjev IA, Popkov VA, Babenko VA, Zorova LD, Pevzner, IB, et al. Lessons from the discovery of mitochondrial fragmentation (fission):a review and update. Cells. 2019; 8(2):175. https://doi.org/10.3390/cells8020175 Gou H, Zhao M, Xu H, Yuan J, He W, Zhu M, et al. CSFV induced mitochondrial fission and mitophagy to inhibit apoptosis. Oncotarget. 2017; 8(24):39382. https://doi.org/10.18632/oncotarget.17030 Jingjing Pei, Jieru Deng, Zuodong Ye, Jiaying Wang, Hongchao Gou, Wenjun Liu, et al. Absence of autophagy promotes apoptosis by modulating the ROS-dependent RLR signaling pathway in classical swine fever virus infected cells. Autophagy. 2016; 12(10):1738-1758. https://doi.org/10.1080/15548627.2016.1196318 Rehwinkel J, Gack MU. RIG-I-like receptors: their regulation and roles in RNA sensing. Nat Rev Immunol. 2020; 20(9):537-551. https://doi.org/10.1038/s41577-020-0288-3 Yuan J, Zhu M, Deng S, Fan S, Xu H, Liao J, et al. Classical swine fever virus induces pyroptosis in the peripheral lymphoid organs of infected pigs. Virus Res. 2018; 250:37-42. https://doi.org/10.1016/j.virusres.2018.04.004 Ma SM, Mao Q, Yi L, Zhao MQ, Chen JD. Apoptosis, autophagy, and Pyroptosis: immune escape strategies for persistent infection and pathogenesis of classical swine fever virus. Pathogens. 2019; 8(4):239. https://doi.org/10.3390/pathogens8040239 Sborgi L, Rühl S, Mulvihill E, Pipercevic J, Heilig R, Stahlberg H, et al. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J. 2016; 35(16):1766-1778. https://doi. org/10.15252/embj.201694696 Fink SL, Cookson BT. Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell. Microbiol 2006; 8(11):1812-1825. https://doi.org/10.1111/j.1462-5822.2006.00751.x Brown VR, Bevins SN. A review of classical swine fever virus and routes of introduction into the United States and the potential for virus establishment. Front Vet Sci. 2018; 5:31. https://doi.org/10.3389/fvets.2018.00031 Coronado L, Perera CL, Rios L, Frías MT, Pérez L. A Critical Review about Different Vaccines against Classical Swine Fever Virus and Their Repercussions in Endemic Regions. Vaccines. 2021; 9(2):154. https:// doi.org/10.3390/vaccines9020154 Xie Z, Pang D, Yuan H, Jiao H, Lu C, Wang K, et al. Genetically modified pigs are protected from classical swine fevervirus. PLOS Pathog. 2018; 14(12):e1007193. https://doi.org/10.1371/journal.ppat.1007193 |
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Salgado Ruíz, Jefersson Stiven82750f90d53627664896e48685233c0cJaramillo-Hernández, Dumar Alexandere4e65ff8a9e48274abf930df640121792023-11-08T13:56:51Z2023-11-08T13:56:51Z2021Salgado-Ruíz, J. S. y Jaramillo-Hernández, D. A. (2021). Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásica. Revista MVZ Córdoba,27(1).0122-0268https://repositorio.unillanos.edu.co/handle/001/31242361Universidad de los LlanosRepositorio Universidad de los Llanoshttps://repositorio.unillanos.edu.co/Incluye figuras.La peste porcina clásica (PPC) es una enfermedad causada por un virus ARN de la familia Flaviviridae, genero Pestivirus conocido como Pestivirus C. En la actualidad se conoce su distribución mundial y es causante de grandes pérdidas económicas en las producciones porcícolas. Sus únicos reservorios naturales son el cerdo y el jabalí. El objetivo de esta revisión es presentar una actualización sobre algunos aspectos relevantes epidemiológicos e inmunopatológicos de la PPC. La PPC es una enfermedad de notificación obligatoria para Colombia y los animales persistentemente infectados son la clave para su diseminación y endemicidad. La infección por el virus de la PPC se caracteriza por coagulación intravascular diseminada, trombocitopenia e inmunosupresión, dependiendo en severidad por la virulencia de las distintas cepas. El virus tiene afinidad por monocitos/macrófagos y células endoteliales vasculares donde tiene la capacidad de inducir diferentes mecanismos celulares que le permiten proliferar y persistir en el animal como lo son: el estrés oxidativo al incrementar los niveles de especies reactivas de oxígeno que genera una disminución de la biodisponibilidad de óxido nítrico; la fisión mitocondrial que permite una supervivencia celular por la inhibición de la apoptosis; y la inmunosupresión debido a la depleción de linfocitos T y B creada por la piroptosis en función de la gasdermina-D en órganos linfoides periféricos que reduce la respuesta inmune humoral y celular. El entendimiento inmunopatológico desde la explicación molecular en la PPC es importante en el aporte conceptual del desarrollo de nuevas estrategias profilácticas y terapéuticas que permitan controlar/ erradicar esta enfermedad.Classical swine fever (CSF) is a disease caused by RNA virus, Flaviviridae family, genus Pestivirus, known as Pestivirus C. At present its worldwide distribution is known and is the cause of great economic losses in pig production. Its only natural reservoirs are pigs and wild boar. The aim of this review is to present an update on some relevant epidemiological and immunopathological aspects of CSF. CSF is a notifiable disease for Colombia and persistently infected animals are the key to its spread and endemicity. CSF virus infection is characterized by disseminated intravascular coagulation, thrombocytopenia, and immunosuppression, depending on severity due to the virulence of the different strains. The virus has affinity for monocytes/macrophages and vascular endothelial cells where it has the ability to induce different cellular mechanisms that allow it to proliferate and persist in the animal, such as: oxidative stress by increasing the levels of reactive oxygen species that generates a decrease of the bioavailability of nitric oxide; mitochondrial fission that allows cell survival by inhibiting apoptosis; and immunosuppression due to the depletion of T and B lymphocytes created by pyroptosis as a function of gasdermin-D in peripheral lymphoid organs that reduces the humoral and cellular immune response. The immunopathological understanding from the molecular explanation in CSF is important in the conceptual contribution of the development of new prophylactic and therapeutic strategies that allow to control/eradicate this disease. Keywords: Communicable diseases; immunology; oxidative stress; pyroptosis; virology (Source:DeCS).12 Páginasapplication/pdfspaUniversidad de Los LlanosVillavicencioDerechos Reservados - Universidad de Los Llanos, 2021https://creativecommons.org/licenses/by-nc-nd/4.0/Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2https://doi.org/10.21897/rmvz.2361Algunas consideraciones de epidemiología e inmunopatología de la peste porcina clásicaArtículo de revistainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Texthttp://purl.org/coar/version/c_970fb48d4fbd8a85Kleiboeker SB. Swine fever: classical swine fever and African swine fever. 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PLOS Pathog. 2018; 14(12):e1007193. https://doi.org/10.1371/journal.ppat.10071931Vol. 27Revista MVZ CórdobaN/APeste porcinaEnfermedad transmisibleInmunologíaEstrés oxidativoPiroptosisCommunicable diseasesImmunologyOxidative stressPyroptosisPublicationORIGINALAnexo 1Anexo 1Carta de autorizaciónapplication/pdf144689https://dspace7-unillanos.metacatalogo.org/bitstreams/87122a59-e1f7-4107-8dd5-ed1568f6eb90/download9007beb11f2a2437279bb367bc9a1bbdMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-814775https://dspace7-unillanos.metacatalogo.org/bitstreams/70102441-2f7b-4b3a-b7a7-adf36dcaea82/downloadf661acf14bedbf9f5d13897a0387e751MD56TEXTAnexo 1.txtAnexo 1.txtExtracted texttext/plain2136https://dspace7-unillanos.metacatalogo.org/bitstreams/0734cd78-f3f6-47d8-b499-636b34eb6252/download0ffa5dba2ecdb9f3ba2ad171a97d0776MD57THUMBNAILAnexo 1.jpgAnexo 1.jpgGenerated 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Llanosrepositorio@unillanos.edu.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