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The dark-light transition experiments were carried out as described previously 23

doi: 10.1152/ajpgi.00072.2010 6 BlumbergR.ChoJ.LewisJ.WuG

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The sequential clinical presentation of smallpox, starting from exposure, to asymptomatic viral replication with two early viremias, to prodroma, to rash, and then to complications, or recovery, or demise reveals unique stepwise pathogenesis: blocked initial host defense cellular reactions accompanied by unimpeded and asymptomatic viral replication with viremias, and later on, cascades of severe unregulated inflammatory reactions, localization of adherent Variola-laden leucocytes within dermal capillaries, leucocyte diapedesis from the capillaries to infect the skin, destructive rash, toxemias, circulating immune complexes with soluble Variola antigens, and complement activation, among others