The Localization of Influenza Virus in the Respiratory Tract of Ferrets: the Importance of Early Replication Events in Determining Tissue Specificity

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Abstract
Summary In investigating the reasons for the greater susceptibility of upper respiratory tissue of ferrets to influenza virus infection, comparisons were made of the early events in virus replication in organ cultures of fresh lung (low susceptibility) and fresh nasal turbinates and maintained lung (high susceptibility). The lower susceptibility of fresh lung was reflected in a higher minimal infectious dose (MID50) and lower virus yields at 24 h except with very high inocula when yields for the three tissues were similar. Fresh and maintained lung had similar quantities of alveolar surfactant. Extracts of fresh lung had only weak inhibitory activity on virus replication in organ cultures of all three tissues. Virus adsorption to organ cultures was similar for the three tissues and equal to that shown by frozen and thawed tissue. Estimates of virus particles adsorbed to a standard length of cell membrane in electron micrographs, indicated some differences in numbers of virus receptors on different cells and an increase of receptors with maintenance. However, this occurred for nasal turbinates as well as for lung; thus the differences in receptors did not correlate with the differences in susceptibilities between the tissues. The proportions and numbers of susceptible cells were similar for the various tissues in cell suspensions prepared by two methods from organ cultures inoculated with high virus inocula and stained with fluorescent antibody. With small inocula, which resulted in large differences in virus yield at 24 h from the three tissues, the numbers of cells initially infected were only slightly different. This indicated that the differences in susceptibility were not primarily determined by differences in initiation of infection of susceptible cells. It is suggested that the quantity or quality of virus released at the first cycle, in relation to the ease of initiating the second cycle of infection, is the dominant factor in tissue susceptibility.