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Title:   Author  item
                                            Pantin Jackwood, Maryitem
                                            LEE, CHAN-WON - OHIO STATE UNIVERSITYitem
                                            Kapczynski, Darrellitem
                                            Sarmento, Lucianaitem
                                            Wasilenko, Jamieitem
                                            Spackman, Ericaitem
                                            Suarez, David
  Submitted to: Options for the Control of Influenza Conference
                                    Publication Type: Proceedings
                                    Publication Acceptance Date: 7/10/2007
                                    Publication  Date: 9/19/2008
                                    Citation: Pantin-Jackwood, M., Lee, C-W, Kapczynski, D.R., Sarmento, S., Wasilenko, J.L., Spackman, E., Suarez, D.L. 2008. Pathogenicity of H5N1 avian influenza virus reassortants in chickens. In proceedings of Options for the Control of Influenza VI, June 17-23, 2007. Toronto, ON. Canada. p. 546-548.      Interpretive Summary: Chickens infected with H5N1 highly pathogenic avian influenza viruses suffer from severe disease and high mortality.  Reverse genetics was used to find out which viral gene or genes contributed to the pathogenicity of these viruses in chickens, helping to identify the genes responsible for cell tropism and replication efficiency.  Intranasal inoculation of two week-old chickens with one of the recombinant avian influenza virus, rEgret/HK/02, resulted in 100% mortality and high viral load in tissues.  Inoculation of chickens with another recombinant virus, rCk/Indonesia/03, only produced 50% mortality and less virus was detected in tissues.  Reassortant viruses combining genes of the mentioned viruses showed that swapping the hemagglutinin and PB2 genes greatly affected pathogenicity, which was reflected in differences in mortality, viral replication, and spread in tissues.  The NS gene also affected viral replication and spread in tissues; however, no effect on mortality was observed.  Differences in cytokine levels in lung and spleen were observed, indicating a role of the innate immune response on the outcome of infection.
                                Technical Abstract: Highly pathogenic H5N1 avian influenza viruses produce severe disease and mortality in chickens.  Identification of viral genes important for cell tropism and replication efficiency helps identify virulence factors.  To determine which viral gene or genes contribute to the virulence of H5N1 avian influenza viruses in chickens, we used reverse genetics to generate single-gene recombinant viruses and examined their pathogenicity in chickens.  Intranasal inoculation of two week-old chickens with the recombinant avian influenza virus rEgret/HK/02 resulted in 100% mortality and high viral titers in tissues.  Inoculation of chickens with rCk/Indonesia/03 produced only 50% mortality with significantly less viral replication in tissues.  Reassortants combining genes of the mentioned viruses demonstrated that exchanging the hemagglutinin and PB2 genes considerably affected pathogenicity; this was reflected in differences in mortality, viral replication, and spread in tissues.  The NS gene also had an effect on viral replication and spread in tissues; however, no effect on mortality was observed.  Differences in mRNA cytokine levels in lung and spleen were observed among the different groups, indicating a role of the innate immune response on the outcome of infection.


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