Experimental Infection with Influenza a Virus in Mice

Following intranasal inoculation of influenza A virus (strain PR8) there is a rapid increase of the virus in the lungs which with large doses reaches a maximum within 24 hours. With smaller doses, although the proportional increase is greater, the maximum concentration is not reached until 48 hours following inoculation. If a lethal dose is administered, the ultimate concentration of the virus in the lungs is the same, irrespective of the size of the dose. If a sublethal dose is given, the titer of the virus in the lungs does not achieve the titer reached in mice receiving a lethal dose. Within 48 hours following inoculation of a sublethal dose the lungs of a mouse may contain at least 76,000 M.L.D., yet the mouse survives. The intranasal instillation of sterile fluid (distilled water, varying concentrations of NaCl, broth, or 10 per cent normal serum) into a mouse sublethally infected produces a sharp rise in the virus content of the lung usually followed by death within 3 to 8 days. If, however, the instillate consists of 10 per cent immune serum, there is no rise in the virus titer, and no apparent harm results from the instillation. The implications of these phenomena are discussed and an hypothesis presented to explain their occurrence.