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Title: Pathogenesis of H5N1 influenza virus infections in mice and ferret models differ between respiratory and digestive system exposure

Author
item Lipatov, Aleksandr
item KWON, YONG KUK - USDA-FAS-OIRP-RSED
item Pantin Jackwood, Mary
item Swayne, David

Submitted to: Journal of Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/30/2008
Publication Date: 2/9/2009
Citation: Lipatov, A.S., Kwon, Y., Pantin Jackwood, M.J., Swayne, D.E. 2009. Pathogenesis of H5N1 influenza virus infections in mice and ferret models differs according to respiratory tract or digestive tract system exposure. Journal of Infectious Diseases. 199:717-725.

Interpretive Summary: Field data suggests H5N1 high pathogenicity avian influenza (HPAI) viruses are transmitted through and predominantly affect the respiratory system of mammals. However, some data suggests the digestive system can be involved and consumption of infected raw products could initiate infections. Using a ferret animal model, we determined that three H5N1 viruses could be transmitted through eating infected raw chicken meat, but the infections were predominately initiated in and affected the respiratory system. The tonsil appeared to be the site of initial infection with subsequent spread to the respiratory tissues. However, with one H5N1 systemic virus strain, A/Vietnam/1203/04, the digestive system was also concurrently affected and the site of initial replication was the small intestines, followed by spread to the liver and pancreas. Our results confirm that consumption of raw H5N1 HPAI virus infected products could initiate infection; as has occurred naturally with tigers, leopards, domestic cats and dogs. However, because humans consume almost exclusively cooked product, foods are unlikely to serve as vehicles of transmission of H5N1 HPAI virus to humans.

Technical Abstract: Background. Epidemiological, clinical and laboratory data suggests H5N1 influenza viruses are transmitted through and predominantly affect the respiratory system of mammals. Some data suggests digestive system involvement. However, direct evidence of alimentary transmission and infection in mammals is lacking. Methods. Infection and pathogenesis of four H5N1 viruses were assessed in mice and ferrets inoculated intranasally or intragastrically with virus in liquid. In addition, ferrets were fed infected raw chicken meat or minced meat administered through gavage tube into the stomach. Results. Only one virus, A/Whooper swan/Mongolia/244/05, was able to infect mice after intragastric inoculation in liquid while no evidence of infection was observed in intragastrically-inoculated ferrets. Ferret consumption of infected meat resulted in respiratory infection only (A/Muscovy duck/Vietnam/209/05 and A/Whooper swan/Mongolia/244/05 viruses) or in both severe respiratory and systemic infection with predominant involvement of liver, pancreas, large and small intestine (A/Vietnam/1203/04 virus). Direct intragastric exposure to infected meat (A/Vietnam/1203/04 virus) resulted in lethal systemic disease mainly affected intestine, liver and pancreas, but lacked lung involvement. Conclusions. Our results demonstrated digestive system exposure to H5N1 influenza viruses could initiate infection either through the tonsil with spread to respiratory tissues, or intestinal infection with spread to the liver and pancreas.