The pig: a model for human infectious diseases

An animal model to study human infectious diseases should accurately reproduce the various aspects of disease. Domestic pigs (Sus scrofa domesticus) are closely related to humans in terms of anatomy, genetics and physiology, and represent an excellent animal model to study various microbial infectious diseases. Indeed, experiments in pigs are much more likely to be predictive of therapeutic treatments in humans than experiments in rodents. In this review, we highlight the numerous advantages of the pig model for infectious disease research and vaccine development and document a few examples of human microbial infectious diseases for which the use of pigs as animal models has contributed to the acquisition of new knowledge to improve both animal and human health.

[1]  L. Saif,et al.  Toll-like receptor and innate cytokine responses induced by lactobacilli colonization and human rotavirus infection in gnotobiotic pigs. , 2009, Veterinary immunology and immunopathology.

[2]  D. Hume,et al.  The mononuclear phagocyte system of the pig as a model for understanding human innate immunity and disease , 2011, Journal of leukocyte biology.

[3]  K. McCullough,et al.  Pathogenesis of granulocytopenia and bone marrow atrophy during classical swine fever involves apoptosis and necrosis of uninfected cells. , 2000, Virology.

[4]  A. Summerfield.  Special issue on porcine immunology: an introduction from the guest editor. , 2009, Developmental and comparative immunology.

[5]  L. Saif,et al.  Virus-specific intestinal IFN-gamma producing T cell responses induced by human rotavirus infection and vaccines are correlated with protection against rotavirus diarrhea in gnotobiotic pigs. , 2008, Vaccine.

[6]  K. McCullough,et al.  The porcine dendritic cell family , 2008, Developmental & Comparative Immunology.

[7]  A trypsin-like serine protease is involved in pseudorabies virus invasion through the basement membrane barrier of porcine nasal respiratory mucosa , 2011, Veterinary research.

[8]  C. Ross,et al.  Antimicrobial host defense peptides in an arteriviral infection: differential peptide expression and virus inactivation. , 2009, Viral immunology.

[9]  C. Ernst,et al.  Human chromosome 3 and pig chromosome 13 show complete synteny conservation but extensive gene-order differences , 1999, Cytogenetic and Genome Research.

[10]  R. Webby,et al.  Pathogenicity of swine influenza viruses possessing an avian or swine-origin PB2 polymerase gene evaluated in mouse and pig models. , 2011, Virology.

[11]  A. Vlasova,et al.  Altered Pathogenesis of Porcine Respiratory Coronavirus in Pigs due to Immunosuppressive Effects of Dexamethasone: Implications for Corticosteroid Use in Treatment of Severe Acute Respiratory Syndrome Coronavirus , 2007, Journal of Virology.

[12]  K. Krawczyński,et al.  Pathogenetic elements of hepatitis E and animal models of HEV infection. , 2011, Virus research.

[13]  H. Salmon,et al.  Membrane markers of the immune cells in swine: an update. , 2008, Veterinary research.

[14]  A. Ljungh,et al.  Staphylococcal Wound Infection in the Pig: Part II. Inoculation, Quantification of Bacteria, and Reproducibility , 1989, Annals of Plastic Surgery.

[15]  Y. Sakoda,et al.  PB2 Protein of a Highly Pathogenic Avian Influenza Virus Strain A/chicken/Yamaguchi/7/2004 (H5N1) Determines Its Replication Potential in Pigs , 2008, Journal of Virology.

[16]  M. Pensaert,et al.  In vivo studies on cytokine involvement during acute viral respiratory disease of swine: troublesome but rewarding , 2002, Veterinary Immunology and Immunopathology.

[17]  K. McCullough,et al.  Dendritic cells--at the front-line of pathogen attack. , 2009, Veterinary immunology and immunopathology.

[18]  F. Clubb,et al.  Swine as Models in Biomedical Research and Toxicology Testing , 2012, Veterinary pathology.

[19]  M. Han,et al.  Porcine Noroviruses Related to Human Noroviruses , 2005, Emerging infectious diseases.

[20]  J. Lunney,et al.  The piglet as a model for B cell and immune system development , 2008, Veterinary Immunology and Immunopathology.

[21]  H. Dawson.  A Comparative Assessment of the Pig, Mouse and Human Genomes: Structural and Functional Analysis of Genes Involved in Immunity and Inflammation , 2011 .

[22]  H. Nauwynck,et al.  Replication of avian, human and swine influenza viruses in porcine respiratory explants and association with sialic acid distribution , 2010, Virology Journal.

[23]  D. Ochs,et al.  Immunodeficiency in young pigs. , 1989, American journal of veterinary research.

[24]  J. Doudna,et al.  Adaptive strategies of the influenza virus polymerase for replication in humans , 2009, Proceedings of the National Academy of Sciences.

[25]  S. Elahi,et al.  The benefits of using diverse animal models for studying pertussis. , 2007, Trends in microbiology.

[26]  J. McCulley,et al.  A pig model of Acanthamoeba keratitis: transmission via contaminated contact lenses. , 1992, Investigative ophthalmology & visual science.

[27]  T. Harkinezhad,et al.  Specific-Pathogen-Free Pigs as an Animal Model for Studying Chlamydia trachomatis Genital Infection , 2005, Infection and Immunity.

[28]  L. Babiuk,et al.  Infection of Newborn Piglets with Bordetella pertussis: a New Model for Pertussis , 2005, Infection and Immunity.

[29]  E. Matisoo-Smith,et al.  Worldwide Phylogeography of Wild Boar Reveals Multiple Centers of Pig Domestication , 2005, Science.

[30]  M. Pensaert,et al.  Correlations between lung proinflammatory cytokine levels, virus replication, and disease after swine influenza virus challenge of vaccination-immune pigs. , 2002, Viral immunology.

[31]  H. Shang,et al.  Light microscopic, electron microscopic, and immunohistochemical comparison of Bama minipig (Sus scrofa domestica) and human skin. , 2010, Comparative medicine.

[32]  L. Babiuk,et al.  Maternal Immunity Provides Protection against Pertussis in Newborn Piglets , 2006, Infection and Immunity.

[33]  Denis Milan,et al.  Design of a High Density SNP Genotyping Assay in the Pig Using SNPs Identified and Characterized by Next Generation Sequencing Technology , 2009, PloS one.

[34]  B. C. Hellerud,et al.  A NEW DYNAMIC PORCINE MODEL OF MENINGOCOCCAL SHOCK , 2009, Shock.

[35]  J. Butler,et al.  The isolator piglet: a model for studying the development of adaptive immunity , 2007, Immunologic research.

[36]  J. Zimmerman,et al.  A review of porcine tonsils in immunity and disease , 2003, Animal Health Research Reviews.

[37]  J. Le Pendu,et al.  Mendelian resistance to human norovirus infections , 2006, Seminars in Immunology.

[38]  J. Nedrud.  Animal models for gastric Helicobacter immunology and vaccine studies. , 1999, FEMS immunology and medical microbiology.

[39]  Jishan Sun,et al.  Antibody Repertoire Development in Fetal and Neonatal Pigs. VII. Characterization of the Preimmune κ Light Chain Repertoire1 , 2004, The Journal of Immunology.

[40]  J. Rogers,et al.  Pig genome sequence - analysis and publication strategy , 2010, BMC Genomics.

[41]  C. Bachert,et al.  Herpes Simplex Virus Type 1 Penetrates the Basement Membrane in Human Nasal Respiratory Mucosa , 2011, PloS one.

[42]  V. Gerdts,et al.  Humoral and cellular factors of maternal immunity in swine. , 2009, Developmental and comparative immunology.

[43]  N. De Regge,et al.  Interferon Alpha Induces Establishment of Alphaherpesvirus Latency in Sensory Neurons In Vitro , 2010, PloS one.

[44]  Y. Berhane,et al.  Animal models of henipavirus infection: a review. , 2009, Veterinary journal.

[45]  E. Wolf,et al.  Transgenic pigs as models for translational biomedical research , 2010, Journal of Molecular Medicine.

[46]  A. K. Hansen,et al.  The use of pigs in neuroscience: Modeling brain disorders , 2007, Neuroscience & Biobehavioral Reviews.

[47]  A. L. Jensen,et al.  A pig model of acute Staphylococcus aureus induced pyemia , 2009, Acta veterinaria Scandinavica.

[48]  G. Gao,et al.  Crystal Structure of Swine Major Histocompatibility Complex Class I SLA-1*0401 and Identification of 2009 Pandemic Swine-Origin Influenza A H1N1 Virus Cytotoxic T Lymphocyte Epitope Peptides , 2011, Journal of Virology.

[49]  H. Jensen,et al.  A non-traumatic Staphylococcus aureus osteomyelitis model in pigs. , 2010, In vivo.

[50]  D. Cooper,et al.  Selected physiologic compatibilities and incompatibilities between human and porcine organ systems , 2006, Xenotransplantation.

[51]  S. Rosenberg,et al.  Transplantation in miniature swine. , 1977, Transplantation proceedings.

[52]  M. Katze,et al.  2009 Pandemic H1N1 Influenza Virus Causes Disease and Upregulation of Genes Related to Inflammatory and Immune Responses, Cell Death, and Lipid Metabolism in Pigs , 2011, Journal of Virology.

[53]  W. Gerner,et al.  Porcine regulatory T cells: mechanisms and T-cell targets of suppression. , 2011, Developmental and comparative immunology.

[54]  M. Murtaugh,et al.  Species specialization in cytokine biology: is interleukin-4 central to the T(H)1-T(H)2 paradigm in swine? , 2009, Developmental and comparative immunology.

[55]  R. Chanock,et al.  Infection immunity of piglets to either VP3 or VP7 outer capsid protein confers resistance to challenge with a virulent rotavirus bearing the corresponding antigen , 1988, Journal of virology.

[56]  L. Babiuk,et al.  Induction, regulation and physiological role of IL-17 secreting helper T-cells isolated from PBMC, thymus, and lung lymphocytes of young pigs. , 2011, Veterinary immunology and immunopathology.

[57]  R. Argenzio,et al.  Villous atrophy, crypt hyperplasia, cellular infiltration, and impaired glucose-Na absorption in enteric cryptosporidiosis of pigs. , 1990, Gastroenterology.

[58]  D. Kelton,et al.  Human Noroviruses in Swine and Cattle , 2007, Emerging infectious diseases.

[59]  Chang-won Lee,et al.  Swine Influenza H1N1 Virus Induces Acute Inflammatory Immune Responses in Pig Lungs: a Potential Animal Model for Human H1N1 Influenza Virus , 2010, Journal of Virology.

[60]  J. Zimmerman,et al.  Immune components in porcine mammary secretions. , 2000, Viral immunology.

[61]  L. Saif,et al.  Pathogenesis of an attenuated and a virulent strain of group A human rotavirus in neonatal gnotobiotic pigs. , 1996, The Journal of general virology.

[62]  L. Saif,et al.  Binding Patterns of Human Norovirus-Like Particles to Buccal and Intestinal Tissues of Gnotobiotic Pigs in Relation to A/H Histo-Blood Group Antigen Expression , 2007, Journal of Virology.

[63]  L. Babiuk,et al.  Approaches to enhancing immune responses stimulated by CpG oligodeoxynucleotides. , 2009, Advanced drug delivery reviews.

[64]  S. Rosenberg,et al.  TRANSPLANTATION IN MINIATURE SWINE: I. Fixation of the Major Histocompatibility Complex , 1976, Transplantation.

[65]  W. Tyler,et al.  A study of the subgross pulmonary anatomy in various mammals , 1961 .

[66]  Sergio Pinto,et al.  Granuloma Encapsulation Is a Key Factor for Containing Tuberculosis Infection in Minipigs , 2010, PloS one.

[67]  J. L. Barra,et al.  Differential interaction of Escherichia coli heat-labile toxin and cholera toxin with pig intestinal brush border glycoproteins depending on their ABH and related blood group antigenic determinants , 1994, Infection and immunity.

[68]  M. Murtaugh,et al.  Inducible nitric oxide synthase expression in porcine immune cells. , 1998, Veterinary immunology and immunopathology.

[69]  K. Dyce,et al.  Textbook of veterinary anatomy , 1987 .

[70]  C. Agustí,et al.  Animal models of ventilator-associated pneumonia , 2009, European Respiratory Journal.

[71]  H. Nauwynck,et al.  Bronchoalveolar Interferon-α, Tumor Necrosis Factor-α, Interleukin-1, and Inflammation during Acute Influenza in Pigs: A Possible Model for Humans? , 1998, The Journal of infectious diseases.

[72]  L. Babiuk,et al.  Infection with Bordetella parapertussis but not Bordetella pertussis causes pertussis-like disease in older pigs. , 2008, The Journal of infectious diseases.

[73]  K. Atanasova,et al.  Cytokines and acute phase proteins associated with acute swine influenza infection in pigs , 2010, The Veterinary Journal.

[74]  Jane Rogers,et al.  Lessons learned from the initial sequencing of the pig genome: comparative analysis of an 8 Mb region of pig chromosome 17 , 2007, Genome Biology.

[75]  R. Coffman,et al.  TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. , 1989, Annual review of immunology.

[76]  L. Saif,et al.  The gnotobiotic piglet as a model for studies of disease pathogenesis and immunity to human rotaviruses. , 1996, Archives of virology. Supplementum.

[77]  K. Chaloner,et al.  Antibody repertoire development in fetal and neonatal piglets XXI. Usage of most VH genes remains constant during fetal and postnatal development. , 2011, Molecular immunology.

[78]  Peter B Jahrling,et al.  Exotic emerging viral diseases: progress and challenges , 2004, Nature Medicine.