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J. Virol. doi:10.1128/JVI.01667-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Amelioration of Influenza Pathogenesis in Chickens Attributed to the Enhanced Interferon-Inducing Capacity of a Virus with a Truncated NS1 Gene

Southeast Poultry Research Laboratory, ARS/USDA, Athens, Georgia 30605; Department of Molecular and Cell Biology, and Center of Excellence for Vaccine Research, University of Connecticut, U-3125, Storrs, CT 06269

^* To whom correspondence should be addressed. Email: dsuarez{at}seprl.usda.gov.

	Abstract

Avian influenza virus A/TK/OR/71-SEPRL(H7N3) encodes a full length NS1 protein and is a weak inducer of interferon (IFN). A variant, TK/OR/71-delNS1(H7N3), produces a truncated NS1 protein and is a strong inducer of IFN. These otherwise genetically related variants differ 20-fold in their capacity to induce IFN in primary chicken embryo cells, but are similar in their sensitivity to the action of interferon (IFN). Furthermore, the weak IFN-inducing strain actively suppresses IFN induction in cells otherwise programmed to produce it. These phenotypic differences are attributed to the enhanced IFN-inducing capacity that characterizes type A influenza strains which produce defective NS1 protein. The pathogenesis of these two variants was evaluated in 1-day-old and 4-week-old chickens. The cell tropism of both viruses was similar. However, the lesions in chickens produced by the weak IFN-inducer were more severe and differed somewhat in character from those observed for the strong IFN-inducer. Differences in lesions included the nature of inflammation, rate of resolution of the infection, and the extent of viral replication and/or virus dissemination. The amelioration of pathogenesis is attributed to the higher levels of IFN produced by the variant encoding the truncated NS1 protein, and the antiviral state subsequently induced by that IFN. The high titer of virus observed in kidney tissue (10⁹ ELD₅₀/gm) from 1-day-old chickens infected intravenously by the weak IFN-inducing strain is attributed to the capacity of chicken kidney cells to activate the HA fusion peptide along with their unresponsiveness to inducers of IFN as measured in vitro. Thus, the IFN-inducing capacity of AIV appears to be a significant factor in regulating the pathogenesis, virulence, and viral transmission of AIV in chickens. This suggests that the IFN-inducing and IFN induction-suppression phenotypes of AIV should be considered when characterizing strains of influenza virus.

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