Due to the size of the Siemens Trimodal gantry for PET/CT imaging we chose four month old females rather than male ferrets. The pandemic H1N1 isolate KY/180 employed in these studies was isolated from nasal swab sample provided by the Severe Influenza Pneumonia Surveillance project, a clinical study of hospitalized patients with influenza pneumonia in Kentucky. The patient had a severe course of influenza disease and died after 19 days. Sequencing of the HA1 gene from this isolate revealed the D222G mutation, which has been associated with severe disease in human cases [37] [38] [39] [40] . The second passage of the KY/180 seed was employed in the characterization of infection in the female ferrets. The 50% infectious dose in female ferrets was determined to be 10 0.07 TCID 50 (data not shown). In group 1, six ferrets were mock infected with PBS. In group 2, six ferrets were infected intranasally (i.n.) with KY/180 with a 0.5 ml dose of 0.5610 5.7 TCID 50 per naris. Ferrets were monitored for temperature for 10 DPI, and for body weight and clinical symptoms for 28 DPI. Two animals in each group were euthanized on days 2, 14 and 18 to determine virus and HI titers in blood, lung and several additional organs at 2 DPI.