This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Costa-Pereira, A. P.
Right arrow Articles by Kerr, I. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Costa-Pereira, A. P.
Right arrow Articles by Kerr, I. M.

 Previous Article  |  Next Article 

Journal of Virology, September 2002, p. 9060-9068, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9060-9068.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Antiviral Response to Gamma Interferon

Ana P. Costa-Pereira, Timothy M. Williams, Birgit Strobl,,{dagger} Diane Watling, James Briscoe,,{ddagger} and Ian M. Kerr*

Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom

Received 11 April 2002/ Accepted 12 June 2002

A role for alpha/beta interferon (IFN-{alpha}/ß) in the IFN-{gamma} antiviral response has long been suggested. Accordingly, possible roles for autocrine or double-stranded-RNA (dsRNA)-induced IFN-{alpha}/ß in the IFN-{gamma} response were investigated. Use was made of wild-type and a variety of mutant human fibrosarcoma cell lines, including mutant U5A cells, which lack a functional IFN-{alpha}/ß receptor and hence an IFN-{alpha}/ß response. IFN-{gamma} did not induce detectable levels of IFN-{alpha}/ß in any of the cell lines, nor was the IFN-{gamma} response per se dependent on autocrine IFN-{alpha}/ß. On the other hand, a number of responses to dsRNA [poly(I) · poly(C)] and encephalomyocarditis virus were greatly enhanced by IFN-{gamma} pretreatment (priming) of wild-type cells or of mutant cells lacking an IFN-{alpha}/ß response; these include the primary induction of dsRNA-inducible mRNAs, including IFN-ß mRNA, and, to a lesser extent, the dsRNA-mediated activation of the p38 mitogen-activated protein (MAP) kinase(s). IFN-{gamma} priming of mRNA induction by dsRNA is dependent on JAK1 and shows biphasic kinetics, with an initial rapid (<30-min) response being followed by a more substantial effect on overnight incubation. The IFN-{gamma}-primed dsRNA responses appear to be subject to modulation through the p38, phosphatidylinositol 3-kinase, and ERK1/ERK2 MAP kinase pathways. It can be concluded that despite efficient priming of IFN-ß production, the IFN-{alpha}/ß pathways play no significant role in the primary IFN-{gamma} antiviral response in these cell-virus systems. The observed IFN-{gamma} priming of dsRNA responses, on the other hand, will likely play a significant role in combating virus infection in vivo.

* Corresponding author. Mailing address: Cancer Research UK London Research Institute, Lincoln's Inn Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom. Phone: 44 20 7269 3337. Fax: 44 20 7269 3581. E-mail: ian.kerr{at}cancer.org.uk.

{dagger} Present address: Institute of Animal Breeding and Genetics, A-1210 Vienna, Austria.

{ddagger} Present address: Division of Developmental Neurobiology, Howard Hughes Institute, National Institute for Medical Research, London NW7 1AA, United Kingdom.

Journal of Virology, September 2002, p. 9060-9068, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9060-9068.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Baron, M., Davignon, J.-L. (2008). Inhibition of IFN-{gamma}-Induced STAT1 Tyrosine Phosphorylation by Human CMV Is Mediated by SHP2. J. Immunol. 181: 5530-5536 [Abstract] [Full Text]  
  • Austin, B. A., Halford, W. P., Williams, B. R. G., Carr, D. J. J. (2007). Oligoadenylate Synthetase/Protein Kinase R Pathways and {alpha}beta TCR+ T Cells Are Required for Adenovirus Vector: IFN-{gamma} Inhibition of Herpes Simplex Virus-1 in Cornea. J. Immunol. 178: 5166-5172 [Abstract] [Full Text]  
  • Szalay, G., Sauter, M., Hald, J., Weinzierl, A., Kandolf, R., Klingel, K. (2006). Sustained Nitric Oxide Synthesis Contributes to Immunopathology in Ongoing Myocarditis Attributable to Interleukin-10 Disorders. Am. J. Pathol. 169: 2085-2093 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»