5-0.6) (0.5-0.7) (0.6-0.7) (0.5-0.6) pH1N1

0.8 1.0 1.1 1.2 1.3 0.7 (0.7-0.8) (0.9-1.2) (0.9-1.2) (1.1-1.3) (1.0-1.6) (0.6-0.8) H5N1 0.9 1.4 1.7 2.4 ┼ ┼ (0.6-1.2) (1.1-1.7) (1.2-2.2) (2.0-2.7)     Control JIB04 in vitro 0.7 0.7 0.6 0.6 0.6 0.6 (0.7-0.8) (0.6-0.8) (0.6-0.6) (0.6-0.7) (0.6-0.7) (0.5-0.7) Lung damage % H3N2 3.8 2.5 0 0 0 1.3 (0–8.5) (0–5.4)       (0–3.8)   pH1N1 22.5 25.0 40.0 45.0 47.5 25.0   (17.5-27.5) (19.2-30.8) (31.8-48.1) (35.0-55.0) (30.4-64.6) (19.2-30.8) H5N1 25.0 55.0 62.5 77.5 ┼ ┼ (12.1-37.9) (35.9-74.2) (40.3-84.7) (55.3-99.7)     Control 3.8 6.3 6.3 1.3 5.0 3.8 (1.3-6.3) (1.5-11) (1.5-11) (0–3.8) (5–5) (1.3-6.3) Turbinates/nasal concha log TCID50 H3N2 7.0 6.3 5.1 4.8 neg neg (5.5-8.5) (5.4-7.3) (3.9-6.2) (3.4-6.1)     pH1N1 8.2 8.0 7.6 7.0 neg neg (8.0-8.5) (7.7-8.3) (7.0-8.2) (6.2-7.9)     H5N1 4.8 5.0 5.6 4.9 ┼ ┼ (3.5-6.1) (4.4-5.6) (4.1-7.0) (3.4-6.4)     Trachea log TCID50 H3N2 2.4 neg neg neg neg neg (<1.7-3.1)           pH1N1 5.5 5.4 5.9 5.5 neg neg (5.0-6.0) (5.0-5.9) (5.6-6.3) (4.3-6.9)     H5N1 5.5 4.7 5.1 4.7 ┼ ┼ (4.7-6.3) (4.2-5.1) (4.1-6.2) (3.4-6.0) find protocol     Lung log TCID50 H3N2 neg Neg Neg neg neg neg pH1N1 7.5 5.2 5.5 5.6 neg Neg (7.2-7.8) (4.7-5.8) (5.1-6.0) (5.1-6.2)       H5N1 6.6 (6.0-7.2) 5.2 (4.7-5.6) 5.8 (5.5-6.1)

5.2 (4.7-5.6) ┼ ┼ BodyDMXAA molecular weight Weight decrease (+/- SD), relative lung weight, lung damage and viral titers (log TCID50 +/- SD) for lung, turbinates and trachea over time in H3N2, pH1N1 and H5N1 infected ferrets and the control (mock infection). Ferrets infected with the pH1N1 virus showed more severe clinical signs compared to the seasonal H3N2 virus infected ferrets, with PJ34 HCl a body weight decrease around 15% (SD 11.4-18.6%). Viral titers during pH1N1 virus infection also peaked

at 1 dpi, but occurred at similar levels throughout the whole respiratory tract. One ferret in the pH1N1 group developed severe dyspnea. Relative lung weights increased compared to those of the mock infected animals starting from day 1. Their relative lung weights (weight of lung divided by bodyweight multiplied by 100) had increased from 0.6% (SD 0.57-0.65) to 1.3% (SD 1.0-1.6). The lungs of the pH1N1 virus infected ferrets showed up to 70% consolidation by gross pathology. The HPAI-H5N1 virus infected ferrets showed more severe clinical signs with dyspnea leading to hypoxia. On 2.5 dpi, one animal died and one animal was euthanized for ethical reasons. On 3 dpi, another animal died before it could be euthanized. H5N1 virus was predominantly found in the alveoli and viral titers peaked for a longer period, from 1 to 3 dpi.