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Journal of Virology, March 2007, p. 2318-2327, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.01856-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

NS1 Proteins of Avian Influenza A Viruses Can Act as Antagonists of the Human Alpha/Beta Interferon Response{triangledown}

A. Hayman,1,{dagger} S. Comely,2 A. Lackenby,1,2,{ddagger} L. C. S. Hartgroves,1 S. Goodbourn,3 J. W. McCauley,2,§ and W. S. Barclay1*

School of Biological Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, United Kingdom,1 Division of Microbiology, Institute for Animal Health, Compton Laboratory, Berkshire RG20 7NN, United Kingdom,2 Division of Basic Medical Sciences, St. George's, University of London, London SW17 0RE, United Kingdom3

Received 25 August 2006/ Accepted 1 December 2006

Many viruses, including human influenza A virus, have developed strategies for counteracting the host type I interferon (IFN) response. We have explored whether avian influenza viruses were less capable of combating the type I IFN response in mammalian cells, as this might be a determinant of host range restriction. A panel of avian influenza viruses isolated between 1927 and 1997 was assembled. The selected viruses showed variation in their ability to activate the expression of a reporter gene under the control of the IFN-ß promoter and in the levels of IFN induced in mammalian cells. Surprisingly, the avian NS1 proteins expressed alone or in the genetic background of a human influenza virus controlled IFN-ß induction in a manner similar to the NS1 protein of human strains. There was no direct correlation between the IFN-ß induction and replication of avian influenza viruses in human A549 cells. Nevertheless, human cells deficient in the type I IFN system showed enhanced replication of the avian viruses studied, implying that the human type I IFN response limits avian influenza viruses and can contribute to host range restriction.

* Corresponding author. Mailing address: School of Biological Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, United Kingdom. Phone: 44-1189-316671. Fax: 44-1189-316671. E-mail: w.s.barclay{at}reading.ac.uk.

{triangledown} Published ahead of print on 20 December 2006.

{dagger} Present address: Institute of Immunology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Centre, 0027 Oslo, Norway.

{ddagger} Present address: Respiratory Virus Unit, Virus Reference Division, Centre for Infection, Health Protection Agency, 61 Colindale Avenue, London NW9 5EQ, United Kingdom.

§ Present address: Division of Virology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom.

Journal of Virology, March 2007, p. 2318-2327, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.01856-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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