Porcine Respiratory Coronavirus as a SARS Model

Summary

Principal Investigator: Linda Saif
Abstract: Severe acute respiratory syndrome (SARS) is a newly emerging global disease of humans with a major economic impact and significant bioterrorism potential caused by a new strain of coronavirus (CoV). The lung is the target organ related to the disease manifestations, although diarrhea occurs in some patients. Unresolved questions related to SARS pathogenesis include the mechanisms for "superspreaders" and the atypical pneumonia and variable diarrhea induced and the role of polymicrobial infections in the variable severity of SARS. Host immune factors, especially proinflammatory cytokines may play a role in the severe pulmonary damage, as observed in our studies of respiratory disease in pigs. The widespread use of steroids and IFNs for treatment of SARS patients without a clear understanding of their impact on respiratory disease, necessitates studies of their impact in an animal model susceptible to respiratory CoV infection. Although primates are susceptible to SARS CoV, their limited availability and expense hampers comprehensive studies of SARS pathogenesis. In mouse models, the clinicopathological manifestations of CoV or influenza viral infections differ from in humans whereas in pigs they mimic the human disease. The anatomy, physiology and immune system of the pig respiratory tract closely resembles that of man, providing a unique animal model for the study of viral respiratory disease of humans. The porcine respiratory CoV (PRCV), a spike deletion mutant of the enteric CoV transmissible gastroenteritis virus (TGEV), shows striking pathogenetic similarities to SARS CoV in its primary replication in lung. Of interest, PRCV invariably induces similar lung lesions with atypical pneumonia, even in asymptomatic pigs. Our studies suggest that polymicrobial co-infections influence the severity of PRCV infection, lesions and disease via multiple mechanisms. These include the repertoire of proinflammatory cytokines or the cell infiltrates induced in lung, and the multiple cell types infected. Therefore our aim is to determine the influence of steroids and coinfections with respiratory viruses or bacterial derived components (and the cytokines induced) on the severity of a SARS-like respiratory coronavirus (PRCV) infection of swine. Our Specific Aims are: 1) To assess if corticosteroid treatment of PRCV-infected pigs has an impact on cytokines induced by PRCV or acquired immunity to PRCV and the subsequent course of PRCV infection and disease (mimic impact of steroids on SARS patients); 2) To investigate the impact of prior infection with a distantly related (Nidovirales) low pathogenic respiratory viral pathogen (arterivirus, PRRSV) on subsequent PRCV infection and disease (mimic dual SARS CoV and distinct respiratory CoV infections); 3) To explore the impact of initial infection with PRCV followed by subsequent infection with the respiratory viral pathogen swine influenza virus on PRCV infection and disease (mimic dual infections with SARS CoV and influenza); 4) To determine the impact of concurrent infection of pigs with two antigenically related coronaviruses with distinct tissue tropisms (PRCV, respiratory and TGEV, enteric) on generation of PRCV/TGEV recombinants and coronavirus infection and disease (mimic SARS superspeaders with diarrhea); 5) To examine the impact of sequential inoculation of pigs with PRCV followed by bacterial cell wall components on cytokine production and disease (mimic impact of bacterial coinfections on bacterial coinfections on SARS).
Funding Period: 2004-07-01 - 2010-06-30
more information: NIH RePORT

Top Publications

  1. pmc Porcine reproductive and respiratory syndrome virus-induced immunosuppression exacerbates the inflammatory response to porcine respiratory coronavirus in pigs
    Gourapura J Renukaradhya
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691, USA
    Viral Immunol 23:457-66. 2010
  2. pmc Anti-TNF-alpha therapy does not ameliorate disease in a model of acute virus-endotoxin mediated respiratory disease in pigs
    Kalina Atanasova
    Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B 9820 Merelbeke, Belgium
    Vet Immunol Immunopathol 137:12-9. 2010
  3. pmc Lipoteichoic acid from Staphylococcus aureus exacerbates respiratory disease in porcine respiratory coronavirus-infected pigs
    Kalina Atanasova
    Ghent University, Salisburylaan 133, B 9820 Merelbeke, Belgium
    Vet J 188:210-5. 2011
  4. pmc Nitric oxide is elicited and inhibits viral replication in pigs infected with porcine respiratory coronavirus but not porcine reproductive and respiratory syndrome virus
    Kwonil Jung
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
    Vet Immunol Immunopathol 136:335-9. 2010
  5. pmc Comparative pathogenesis of an avian H5N2 and a swine H1N1 influenza virus in pigs
    Annebel De Vleeschauwer
    Laboratory of Virology, Faculty of Veterinary Medicine Ghent University, Merelbeke, Belgium
    PLoS ONE 4:e6662. 2009
  6. pmc Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections
    Kwonil Jung
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, OH 44691, USA
    J Gen Virol 90:2713-23. 2009
  7. pmc Cytokine responses in porcine respiratory coronavirus-infected pigs treated with corticosteroids as a model for severe acute respiratory syndrome
    Xinsheng Zhang
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
    J Virol 82:4420-8. 2008
  8. pmc 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
    Kwonil Jung
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave, Wooster, Ohio 44691, USA
    J Virol 81:13681-93. 2007
  9. ncbi Quasispecies of bovine enteric and respiratory coronaviruses based on complete genome sequences and genetic changes after tissue culture adaptation
    Xinsheng Zhang
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
    Virology 363:1-10. 2007
  10. pmc Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus
    Xinsheng Zhang
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
    Virology 358:424-35. 2007

Scientific Experts

  • Gourapura J Renukaradhya
  • Kristien Van Reeth
  • Kwonil Jung
  • Xinsheng Zhang
  • Kalina Atanasova
  • Linda J Saif
  • Steven Van Gucht
  • Annebel De Vleeschauwer
  • Filip BarbĂ©
  • Yuxin Tang
  • Konstantin P Alekseev
  • Anastasia Vlasova
  • Nagesh Hadya
  • Shiliang Wang
  • Rebecca Halpin
  • Elodie Ghedin
  • Mustafa Hasoksuz
  • David Spiro
  • Daniel Janies
  • Luc Duchateau
  • Ashita Gurnani
  • Thierry van den Berg
  • Ying Fang
  • Thomas Bruun Rasmussen
  • Ase Uttenthal
  • Steven Van Borm
  • Konstantin Alekseev
  • Leandro R Jones
  • Doo Sung Cheon
  • Anastasia N Vlasova
  • Linda Saif
  • Sarah Stollar
  • Maurice Pensaert
  • Eric Cox

Detail Information

Publications11

  1. pmc Porcine reproductive and respiratory syndrome virus-induced immunosuppression exacerbates the inflammatory response to porcine respiratory coronavirus in pigs
    Gourapura J Renukaradhya
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691, USA
    Viral Immunol 23:457-66. 2010
    ..Thus measurements of cytokines and frequencies of immune cells may serve as indicators of the progression of respiratory viral co-infections, and provide more definitive approaches for treatment...
  2. pmc Anti-TNF-alpha therapy does not ameliorate disease in a model of acute virus-endotoxin mediated respiratory disease in pigs
    Kalina Atanasova
    Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B 9820 Merelbeke, Belgium
    Vet Immunol Immunopathol 137:12-9. 2010
    ....
  3. pmc Lipoteichoic acid from Staphylococcus aureus exacerbates respiratory disease in porcine respiratory coronavirus-infected pigs
    Kalina Atanasova
    Ghent University, Salisburylaan 133, B 9820 Merelbeke, Belgium
    Vet J 188:210-5. 2011
    ..Given that Gram-positive bacteria, capable of producing LTA, are commonly found in pig accommodation, the role of this compound in the development of the porcine respiratory disease complex requires further investigation...
  4. pmc Nitric oxide is elicited and inhibits viral replication in pigs infected with porcine respiratory coronavirus but not porcine reproductive and respiratory syndrome virus
    Kwonil Jung
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
    Vet Immunol Immunopathol 136:335-9. 2010
    ..Thus, NO may play a role in innate immunity to respiratory CoV infections by inhibiting viral replication...
  5. pmc Comparative pathogenesis of an avian H5N2 and a swine H1N1 influenza virus in pigs
    Annebel De Vleeschauwer
    Laboratory of Virology, Faculty of Veterinary Medicine Ghent University, Merelbeke, Belgium
    PLoS ONE 4:e6662. 2009
    ....
  6. pmc Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections
    Kwonil Jung
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, OH 44691, USA
    J Gen Virol 90:2713-23. 2009
    ..This study provides new insights into host-pathogen interactions related to co-infection by CoVs and other respiratory viruses...
  7. pmc Cytokine responses in porcine respiratory coronavirus-infected pigs treated with corticosteroids as a model for severe acute respiratory syndrome
    Xinsheng Zhang
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
    J Virol 82:4420-8. 2008
    ..Our findings suggest that future glucocorticoid treatment of SARS patients should be reconsidered in the context of potential local immunosuppression of immune responses in lung and systemic Th1 cytokine-biased suppression...
  8. pmc 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
    Kwonil Jung
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave, Wooster, Ohio 44691, USA
    J Virol 81:13681-93. 2007
    ..These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects...
  9. ncbi Quasispecies of bovine enteric and respiratory coronaviruses based on complete genome sequences and genetic changes after tissue culture adaptation
    Xinsheng Zhang
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
    Virology 363:1-10. 2007
    ..These data suggest that BCoV evolves through quasispecies development, and that enteric BCoV isolates are more prone to genetic changes and may mutate to resemble respiratory BCoV strains after tissue culture passage...
  10. pmc Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus
    Xinsheng Zhang
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
    Virology 358:424-35. 2007
    ..Phylogenetic analyses showed that virulence is an evolutionarily labile trait in TGEV and that TGEV strains as a group share a common ancestor with PRCV...
  11. ncbi Effect of porcine respiratory coronavirus infection on lipopolysaccharide recognition proteins and haptoglobin levels in the lungs
    Steven Van Gucht
    Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B 9820 Merelbeke, Belgium
    Microbes Infect 8:1492-501. 2006
    ..The marked increases in LBP, CD14 and haptoglobin were not correlated with the extent of the LPS response...