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Title:   Author  item
                                            Pantin Jackwood, Maryitem
                                            Smith, Dianeitem
                                            Wasilenko, Jamieitem
                                            Cagle, Caranitem
                                            Shepherd, Ericitem
                                            Sarmento, Lucianaitem
                                            Kapczynski, Darrellitem
                                            Afonso, Claudio
  Submitted to: Virus Research
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 4/27/2012
                                    Publication  Date: 7/16/2012
                                    Citation: Pantin Jackwood, M.J., Smith, D.M., Wasilenko, J.L., Cagle, C.A., Shepherd, E.M., Sarmento, L., Kapczynski, D.R., Afonso, C.L. 2012. Effect of age on pathogenesis and innate immune responses in Pekin ducks infected with different H5N1 highly pathogenic avian influenza viruses. Virus Research. 167:196-206.Interpretive Summary: The H5N1 highly pathogenic avian influenza (HPAI) viruses are widespread in poultry in Asia and have also spread to countries in the Middle East, Europe and Africa, causing great losses to the poultry industry.  Ducks have been implicated in the dissemination of H5N1 HPAI viruses.  The H5N1 HPAI viruses have changed from producing mild respiratory infections to causing severe disease and death in ducks.  The objective of this study was to examine host-virus interactions that occur during H5N1 HPAI infection in ducks.  Two and five week-old Pekin ducks were infected with three different H5N1 HPAI viruses.  Virus-induced pathology ranged from no clinical signs to severe disease and mortality, with the 2-week-old ducks being more severely affected by the more virulent viruses.  Also, reverse-transcriptase polymerase chain reaction assays were conducted to determine the expression of innate immune-related genes in the spleen and lungs of the ducks.  Gene expression profiles in duck tissues after H5N1 HPAI virus infection varied depending on the virus given and also the age of the ducks.  A stronger pro-inflammatory response was observed with the more pathogenic viruses and in older ducks.  This information will help to better understand host responses to AI virus infection and improve methods of control for AI including vaccination.
                                Technical Abstract: The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in domestic ducks varies between different viruses and is affected by the age of the ducks, with younger ducks presenting more severe disease.  In order to better understand the pathobiology of H5N1 HPAI in ducks, including the role of host responses, 2- and 5-week-old Pekin ducks were infected with three different H5N1 HPAI viruses.  Virus-induced pathology ranged from no clinical signs to severe disease and mortality, with the 2-week-old ducks being more severely affected by the more virulent viruses.  However, these more virulent viruses induced higher body temperatures in the 5-week-old ducks than in the 2-week-old ducks, indicating possible differences in innate immune responses.  To analyze the ducks host responses to H5N1 HPAI virus infection, expression of innate immune-related genes was measured in the spleens and lungs of infected ducks at the peak of virus infection.  IFN-alpha, RIG-I, and IL-6 RNA levels were increased in spleens regardless of the virus given and the age of the ducks, however differences were observed in the levels of up-regulation of IFN-alpha and RIG-I between the 2- and the 5-week-old ducks with the more virulent virus.  Differences in IL-2 gene expression were also observed.  In the lungs, the levels of cytokine RNA were lower than in the spleen, with mostly up-regulation of RIG-I and IL-6 and down-regulation of IFN-alpha and IL-2, but no significant difference between the 2- and the 5-week-old ducks.  The differences observed in the innate immune responses to infection with H5N1 HPAI viruses could explain in part the differences observed in pathogenicity between the 2- and 5-week-old ducks, however earlier time points after infection and additional cytokines should be examined.


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