Because of the marked morphological abnormality of the nasal respiratory epithelium in ferrets recovering from epidemic influenza virus infection, attempts were made to determine whether the anatomical changes were associated with functional changes in the epithelial cells. It was found that on the 7th or 8th day after infection, at which time an immature transitional type of epithelium covers the respiratory area, the cells are resistant not only to reinfection with influenza virus but to a severe physicochemical stimulus supplied by iontophoresis or prolonged irrigation with zinc sulfate. Later, as the ciliated columnar cells return, susceptibility to physicochemical injury returns although resistance to influenza virus persists. The ciliated columnar cells are the ones which are damaged by the physicochemical agent while the deeper cells in the regenerating area remain unaffected. 5 weeks after infection the epithelium is anatomically normal but tissue resistance to zinc sulfate is still present to some degree as evidenced by foci of undamaged cells remaining after ionization.
The olfactory epithelium which is undamaged by the PR8 strain of epidemic influenza virus also becomes resistant to ionization after infection. As soon as the respiratory epithelium exhibits any loss of resistance to zinc sulfate the chemical produces complete necrosis of the olfactory area.
The refractory state to physicochemical agents exhibited by the regenerating nasal mucosa of the ferret after influenza virus infection is thought to be a non-specific resistant state, significant for a time at least, in the mechanism of immunity to influenza virus.