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Journal of Virology, March 2005, p. 2880-2890, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2880-2890.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Interferon Induction and/or Production and Its Suppression by Influenza A Viruses{dagger}

Philip I. Marcus,1,2* Jillian M. Rojek,2,3,{ddagger} and Margaret J. Sekellick1,2

Department of Molecular and Cell Biology,1 Department of Pathobiology and Veterinary Science,2 Center for Excellence in Vaccine Research, University of Connecticut, Storrs, Connecticut3

Received 12 August 2004/ Accepted 18 November 2004

Developmentally aged chicken embryo cells which hyperproduce interferon (IFN) when induced were used to quantify IFN production and its suppression by eight strains of type A influenza viruses (AIV). Over 90% of the IFN-inducing or IFN induction-suppressing activity of AIV populations resided in noninfectious particles. The IFN-inducer moiety of AIV appears to preexist in, or be generated by, virions termed IFN-inducing particles (IFP) and was detectable under conditions in which a single molecule of double-stranded RNA introduced into a cell via endocytosis induced IFN, whereas single-stranded RNA did not. Some AIV strains suppressed IFN production, an activity that resided in a noninfectious virion termed an IFN induction-suppressing particle (ISP). The ISP phenotype was dominant over the IFP phenotype. Strains of AIV varied 100-fold in their capacity to induce IFN. AIV genetically compromised in NS1 expression induced about 20 times more IFN than NS1-competent parental strains. UV irradiation further enhanced the IFN-inducing capacity of AIV up to 100-fold, converting ISP into IFP and IFP into more efficient IFP. AIV is known to prevent IFN induction and/or production by expressing NS1 from a small UV target (gene NS). Evidence is presented for an additional downregulator of IFN production, identified as a large UV target postulated to consist of AIV polymerase genes PB1 + PB2 + PA, through the ensuing action of their cap-snatching endonuclease on pre-IFN-mRNA. The products of both the small and large UV targets act in concert to regulate IFN induction and/or production. Knowledge of the IFP/ISP phenotype may be useful in the development of attenuated AIV strains that maximally induce cytokines favorable to the immune response.

* Corresponding author. Mailing address. Department of Molecular and Cell Biology, 91 North Eagleville Rd., U-3125, University of Connecticut, Storrs, CT 06269. Phone: (860) 486-4254. Fax: (860) 486-5193. E-mail: pmarcus{at}uconn.edu.

{dagger} This is contribution XXIV in a series entitled "Interferon Induction by Viruses."

{ddagger} Present address: Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037

Journal of Virology, March 2005, p. 2880-2890, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2880-2890.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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