Effect of Neuraminidase Inhibitor–Resistant Mutations on Pathogenicity of Clade 2.2 A/Turkey/15/06 (H5N1) Influenza Virus in Ferrets
Figure 4
Replication of recombinant WT, E119A, and N294S viruses in internal organs and histologic changes in the lungs morphology of ferrets infected with these H5N1 viruses.
(A) Virus titers were determined for the lungs (4 lobes tested separately), nasal turbinates, tracheas, small intestines, and livers of ferrets on day 4 post-inoculation. Values (log10EID50/gram tissue) are the mean ± s.d. for two ferrets, unless it is indicated that the virus was detected in one of two ferrets. *, P<0.05, **, P<0.01 compared to WT virus (one-way ANOVA). (B) The images shown are hematoxylin-and-eosin-stained sections of lung tissue from ferrets inoculated with the WT, E119A, and N294S viruses obtained on day 4 post-inoculation. Lung showing bronchiole (b) with epithelial necrosis, intraluminal debris, and inflammatory cells. Lung alveoli (a) of the WT-infected ferrets are lined with interstitial septa (arrows) and have mild to moderate inflammatory cell infiltrates. The lung alveolar architecture of the ferrets inoculated with the E119A mutant is lost due to necrosis of alveolar pneumocytes and the interstitial septa. Lung alveoli of the N294S-infected ferrets are filled with inflammatory cells and hyperplastic pneumocytes obscuring interstitial septa. Magnification, ×20.