Aspects of virulence in ferrets exhibited by influenza virus recombinants of known genetic constitution.

Abstract

The parent viruses and clones 64c and 6 of the A/Puerto Rico/8/34-A/England/939/69 (H3N2) series were examined. Virulence was assessed from 50% infectious dose, replication in the upper respiratory tract, degree of lung infection, and production of fever. Viral infection of the upper respiratory tract declined with onset of the inflammatory response and pyrexia, and restriction of replication in nasal turbinate tissue at pyrexial temperatures correlated with onset and rapidity of decline of infection in the upper respiratory tract. Compared with the H3N2 strains, the HON1 strain of A/Puerto Rico/8/34 stimulated a lower and later inflammatory response, which correlated with a delayed and low fever and, in turn, a high nasal infection that was slow to decline. The differential ability to infect the lung in vivo (clones 64c and 6 more than A/England/ 939/69 and clone 7a more than A/Puerto Rico/8/34 and clone 64d) was not always explained by differences in ability to replicate in lung tissue at normal or pyrexial temperatures. Neither overall virulence nor any particular facet of it can yet be correlated with particular gene pieces. The results are discussed in relation to the virulence of the strains for humans.