title: Highly pathogenic avian influenza viruses do not inhibit interferon synthesis in infected chickens but can override the interferon-induced antiviral state.
abstract: From infection studies with cultured chicken cells and experimental mammalian hosts, it is well known that influenza viruses use the nonstructural protein 1 (NS1) to suppress the synthesis of interferon (IFN). However, our current knowledge regarding the in vivo role of virus-encoded NS1 in chickens is much more limited. Here, we report that highly pathogenic avian influenza viruses of subtypes H5N1 and H7N7 lacking fully functional NS1 genes were attenuated in 5-week-old chickens. Surprisingly, in diseased birds infected with NS1 mutants, the IFN levels were not higher than in diseased birds infected with wild-type virus, suggesting that NS1 cannot suppress IFN gene expression in at least one cell population of infected chickens that produces large amounts of the cytokine in vivo. To address the question of why influenza viruses are highly pathogenic in chickens although they strongly activate the innate immune system, we determined whether recombinant chicken alpha interferon (IFN-α) can inhibit the growth of highly pathogenic avian influenza viruses in cultured chicken cells and whether it can ameliorate virus-induced disease in 5-week-old birds. We found that IFN treatment failed to confer substantial protection against challenge with highly pathogenic viruses, although it was effective against viruses with low pathogenic potential. Taken together, our data demonstrate that preventing the synthesis of IFN is not the primary role of the viral NS1 protein during infection of chickens. Our results further suggest that virus-induced IFN does not contribute substantially to resistance of chickens against highly pathogenic influenza viruses.
authors: Department of Virology, University of Freiburg, Hermann-Herder-Straße 11, D-79104 Freiburg, Germany.
authors: Nicola
authors: N
authors: Penski
authors: Sonja
authors: S
authors: Härtle
authors: Dennis
authors: D
authors: Rubbenstroth
authors: Carsten
authors: C
authors: Krohmann
authors: Nicolas
authors: N
authors: Ruggli
authors: Benjamin
authors: B
authors: Schusser
authors: Michael
authors: M
authors: Pfann
authors: Antje
authors: A
authors: Reuter
authors: Sandra
authors: S
authors: Gohrbandt
authors: Jana
authors: J
authors: Hundt
authors: Jutta
authors: J
authors: Veits
authors: Angele
authors: A
authors: Breithaupt
authors: Georg
authors: G
authors: Kochs
authors: Jürgen
authors: J
authors: Stech
authors: Artur
authors: A
authors: Summerfield
authors: Thomas
authors: T
authors: Vahlenkamp
authors: Bernd
authors: B
authors: Kaspers
authors: Peter
authors: P
authors: Staeheli
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