Reassortment of HA and NA does not affect lethality or pathogenicity in vivo or in cell culture. Survival (A) of ferrets and (B) mice a.i. with VN1203 (n = 2 ferrets, 8 mice) or VN1203-CH58(HA,NA) (n = 3 ferrets, 8 mice). Mean weight change (C) of ferrets and (D) mice ± SE. (E) Mean viral titers from ferret nasal washes ± SE. Dashed line indicates detection limit of 101 EID50/ml. (F) Hematoxylin and eosin–stained sections (20X) of ferret lung, liver and brain 10 d a.i. with VN1203-CH58(HA,NA). Lung (top left) shows bronchiole (*) with epithelial hyperplasia (↑), necrotic debris in lumen and inflammatory cells in alveoli (A). Liver (top right) shows disrupted parenchyma with vacuolated hepatocytes associated with hemorrhage (*). Monocytes (▴) surround parenchyma and hyperplastic biliary cells (↑) extend into parenchyma. Brain (bottom left) shows perivascular inflammatory cells (↑), hypercellular neuropil with capillary endothelial hyperplasia (▴), gliosis and monocytes. Brain region (bottom right) with liquefactive necrosis and foamy macrophages (gitter cells, ▴) and perivascular monocytes (↑). Bar, 40 μm. (G) Plaque formation after virus titration on MDCK cells.