|Belser, Jessica -|
|Wadford, Debra -|
|Pappas, Claudia -|
|Gustin, Kortney -|
|Maines, Taronna -|
|Pearce, Melissa -|
|Zeng, Hui -|
|Katz, Jacqueline -|
|Tumpey, Terrence -|
Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 15, 2010
Publication Date: May 1, 2010
Repository URL: http://handle.nal.usda.gov/10113/44606
Citation: Belser, J.A., Wadford, D.A., Pappas, C., Gustin, K.M., Maines, T.R., Pearce, M.B., Zeng, H., Swayne, D.E., Pantin Jackwood, M.J., Katz, J.M., Tumpey, T.M. 2010. Pathogenesis of pandemic influenza A (H1N1) and triple-reassortant swine influenza A (H1) viruses in mice. Journal of Virology. 84(9):4194-4203. Interpretive Summary: The pandemic H1N1 influenza virus of 2009 (2009 H1N1) continues to cause illness worldwide in humans, primarily in younger age groups. To better understand the disease producing ability of these viruses, we used a mouse model intranasally exposed to influenza, and compared the 2009 H1N1 with H5N1 high pathogenicity avian influenza (HPAI) virus, human seasonal H1N1 influenza virus and a swine influenza virus. All 2009 H1N1 viruses grew in the lungs, but did not cause death and did not spread to other organs. The disease produced by 2009 H1N1 was less severe than produced with swine influenza and H5N1 HPAI viruses. Taken together, these studies demonstrate that the 2009 H1N1 viruses exhibited milder ability to produce disease than HPAI viruses.
Technical Abstract: The pandemic H1N1 virus of 2009 (2009 H1N1) continues to cause illness worldwide, primarily in younger age groups. To better understand the pathogenesis of these viruses in mammals, we used a mouse model to evaluate the relative virulence of selected 2009 H1N1 viruses and compared them to a representative triple-reassortant swine influenza virus that has circulated in pigs in the United States for over a decade preceding the current pandemic. Additional comparisons were made with the reconstructed 1918 virus, a 1976 H1N1 swine influenza virus, and a highly pathogenic H5N1 virus. Mice were inoculated intranasally with each virus and monitored for morbidity, mortality, viral replication, hemostatic parameters, and cytokine production. All 2009 H1N1 viruses replicated efficiently in the lungs of mice and possessed a high degree of infectivity, but did not cause lethal disease or exhibit extrapulmonary virus spread. Transient weight loss, lymphopenia, and proinflammatory cytokine and chemokine production were present following 2009 H1N1 virus infection, but these levels were generally muted compared with a triple-reassortant swine virus and a virus of the H5N1 subtype. 2009 H1N1 viruses isolated from fatal cases did not demonstrate enhanced virulence in this model compared with isolates from mild human cases. Taken together, these studies demonstrate that the 2009 H1N1 viruses exhibited mild to moderate virulence in mice compared with highly pathogenic viruses.