Hemorrhagic Encephalopathy in Chicken Embryos Infected with Influenza Virus

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Summary Prior allantoic infection with homologous or heterologous influenza viruses, or Newcastle disease virus, protected chicken embryos against the hemorrhagic and lethal effects of neurotropic (NWS) influenza virus inoculated intravenously. The titers of NWS virus in brains of protected embryos were appreciably lower than those in fully susceptible controls, suggesting that the protective effect of prior allantoic infection was related to inhibition of NWS virus multiplication. The refractory state to intravenous challenge with NWS virus did not depend on the amount of interfering virus inoculated intra-allantoically but did require that active allantoic infection be established 8 to 16 hr prior to intravenous challenge. Intra-allantoic inoculation of myxovirus inactivated by heat or u.v. irradiation, or neutralized by immune serum, did not enhance resistance to NWS virus challenge. The small quantity of infectious virus disseminated from the allantoic site of infection to the tissues of the embryo seems insufficient to account for interference with NWS virus multiplication. However, multiple intravenous or intra-allantoic injections of infected allantoic fluid, freed of infectious influenza virus by centrifugation and heating, protected embryos against hemorrhagic encephalopathy. These studies are consistent with the hypothesis that the protective effect of prior allantoic infection is related to in vivo production of an interferon that gains access to the embryonic circulation from the infected allantois.