The behaviour in ferrets of two closely related clones of influenza virus of differing virulence for man.

Clones 7a and 64d of the recombinant influenza virus A/PR/8/34-A/England/939/69(H3N2) which are of different virulence for man as judged by clinical score (7a more virulent than 64d) showed similar differences in ferrets. With intranasal inoculation the approximate 50% minimal infectious doses of both clones were similar (between 10(0) and 10(2) EID(50)) as were their titres in nasal washes 24 h after inoculation and the histologically evident damage they caused in the nasal turbinates. However, clone 7a persisted in the nasal washes more than 64d and produced a more prolonged pyrexia. Furthermore, 7a consistently produced a lung infection which was produced only occasionally by 64d and then to a lesser extent than 7a. In contrast to nasal mucosa, histological damage in the lung was slight with both strains. Differences in replication of 7a and 64d in organ cultures of nasal turbinates appeared only after 24 h incubation. They were not sufficiently large to explain the markedly superior ability of 7a to persist in the nasal tract in vivo. This persistence, which coincides with the production of pyrexia, may be due to a greater ability of 7a to resist induced systemic host defences. Spasmodic isolations of infective virus of both clones were made from extra-respiratory tissues such as liver, spleen and kidney.