Differential Distribution of Virus and Histological Damage in the Lower Respiratory Tract of Ferrets Infected with Influenza Viruses of Differing Virulence

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Abstract
Summary The distribution of four strains of influenza virus [A/PR/8/34 (H0N1) and clone 64d (attenuated for ferrets) and clones 64c and 7a (virulent for ferrets) of the recombinant virus A/PR/8/34-A/England/939/69 (H3N2)] in the lower respiratory tract (trachea, bronchi and the hilar, intermediate and outer alveolar zones of the lung) of ferrets was monitored daily for 4 days after intranasal inoculation. On day 1, some animals had high virus titres in all the tissues but in other animals virus was undetectable, irrespective of the virus strain. Two days after inoculation increase of virus contents of all tissues tended to be restricted. On days 3 and 4, the virulent clones (64c and 7a), in contrast to the attenuated strains (A/PR/8/34 and clone 64d), consistently infected the lower respiratory tissues. However, for all infected animals the virus contents of the hilar zones of the lungs were higher than those in the intermediate zones, while the alveolar zones were relatively free from virus. Quantitative estimations of the mild histological damage occurring in the lower respiratory tract 3 to 6 days after inoculation also indicated that bronchial and bronchiolar tissue were more susceptible to influenza virus than alveolar tissue and that clones 64c and 7a produced more damage than the other two strains. In agreement with the relative viral contents of clones 64c and 7a in the bronchi and in the hilar and intermediate zones of the lung, clone 64c produced more damage than clone 7a in the bronchi and less in the bronchioles of the lung parenchyma.