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The Origins of Pandemic Influenza — Lessons from the 1918 Virus (November 24, 2005) @I_Am_JohnCullen @LmBubba The characterization of the recovered 1918 virus in tissue culture and mice reveals at least two unique qualities. This virus is able to replicate and form plaques on tissue-culture monolayers in the absence of the protease trypsin. Normally, a protease such as trypsin is required to activate the hemagglutinin in order to initiate the infection of tissue culture, but the 1918 virus can activate its own hemagglutinin through the action of neuraminidase, either directly or indirectly (possibly by neuraminidase's binding of a host protease). The exact mechanism by which the neuraminidase takes on the protease activity has not been determined. The vigorous release of cytokines in mice infected with the 1918 influenza virus is associated with rapid onset of pulmonary disease and death. https://www.nejm.org/doi/full/10.1056/NEJMp058281