The relation of the concentration of unadapted and adapted influenza virus in the mouse lung to the death or survival of the infected host.

An influenza virus usually requires from 2 to 5 or more serial passages in mice before it becomes sufficiently adapted to its host to cause death, or even extensive pulmonary lesions. But the mouse-unadapted (egg) line of the Cam strain of influenza A prime virus is capable of producing a fatal pneumonia in mice that is grossly indistinguishable from the pneumonia produced by the adapted line of that same virus that had been repeatedly passed in the mouse lung (Sugg, 1949a). However, the unadapted line does not possess all the attributes of a mouse-adapted virus; in contrast to the high degree of virulence possessed by the latter, relatively large amounts of the unadapted line must be introduced into the lungs to produce death, and, more important, suspensions prepared from those lungs fail to produce detectable lesions when passed to normal mice by the intranasal route. Hence, it seemed likely that a comparison of the unadapted and adapted Cam viruses, in respect to the events that take place following the introduction of virus into the mouse lung, might yield information in regard to the properties of an influenza virus that endow it with mouse virulence. Such a comparison was therefore made, and the results of those experiments form the basis of the present report. A few experiments have been reported that compare the multiplication of mouse-unadapted and adapted influenza virus in the mouse lung. During the adaptation of three strains of influenza A virus to mice, Hirst (1947) determined the egg-infectious titer of each of the passage materials, which consisted of lung preparations harvested 3 or 4 days after intranasal inoculation. He reported that mouse unadapted (avirulent) virus multiplied to the same maximum egg-infectious titer in that tissue as the mouse-adapted passage of the same virus. Wang (1948) compared the rate of multiplication of the unadapted and adapted lines of the Rhodes strain of influenza A prime virus by determining both the egginfectious and hemagglutination titers at repeated intervals after intranasal inoculation. Wang found that the mouse-adapted line reached a much higher hemagglutination titer in the lung than did the unadapted line, but stated that the egg-infectious titers attained by the two viruses at the peak of their growth were not markedly different.