Modulation of the severity of highly pathogenic H5N1 influenza in chickens previously inoculated with Israeli H9N2 influenza viruses

The continued evolution of H9N2 and H5N1 viruses and their spread and re-emergence across Eurasia raise concern that prior H9N2 virus infection may limit the detection of subsequent H5N1 infection in gallinaceous poultry by attenuating the severity of disease. We show that H9N2 viruses isolated from Israeli turkeys during 2000-2004 were antigenically and genetically distinguishable. These three H9N2 viruses caused no overt signs of disease in chickens. The 2004 isolate replicated and spread most efficiently, and chickens previously inoculated with this H9N2 virus showed 90%-100% survival after inoculation 1 to 35 days later with lethal H5N1 virus. Chickens that survived did not show signs of disease but did shed lethal H5N1 virus from the cloaca. The modulation of survivability was time-dependent; the effect was maximal 5 days after H9N2 inoculation. These findings suggest that co-circulation of H9N2 viruses can contribute to the spread of lethal H5N1 viruses.