Sensitivity to pyrexial temperatures: a factor contributing to virulence differences between two clones of influenza virus.

The influence of pyrexia on the differential persistence of a virulent and an attenuated clone of influenza virus in the respiratory tract of ferrets has been further studied. Clone 64d, an attenuated clone of a recombinant virus (A/PR/8/34-A/England/939/69 (H3N2)) grown in organ cultures of ferret nasal turbinates, was inactivated at pyrexial temperatures more readily than a virulent Clone 7a. In addition, replication of Clone 64d was restricted at pyrexial temperatures to a greater extent than that of Clone 7a in organ cultures of both ferret nasal turbinate and lung tissue. The greater adverse effects of pyrexial temperatures on Clone 64d appears to explain the earlier reduction of upper respiratory tract infection seen in ferrets infected with this attenuated clone. Also, the differential influence of pyrexial temperatures may be the reason for the virtual lack of lung infection with Clone 64d in vivo in contrast to the consistent infection found with Clone 7a. The relevance of these findings to human infection and to markers of attenuation of influenza virus is discussed.