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Journal of Virology, August 2004, p. 8219-8228, Vol. 78, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.15.8219-8228.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Characterization of the Murine Alpha Interferon Gene Family

Vincent van Pesch,1 Hanane Lanaya,1,{dagger} Jean-Christophe Renauld,2 and Thomas Michiels1*

Université Catholique de Louvain, Christian de Duve Institute of Cellular Pathology, Microbial Pathogenesis Unit, MIPA-VIRO 74-49,1 Unit of Experimental Medicine, Ludwig Institute for Cancer Research and Université Catholique de Louvain, B-1200 Brussels, Belgium2

Received 24 December 2003/ Accepted 17 March 2004

Mouse and human genomes carry more than a dozen genes coding for closely related alpha interferon (IFN-{alpha}) subtypes. IFN-{alpha}, as well as IFN-ß, IFN-{kappa}, IFN-{varepsilon}, and limitin, are thought to bind the same receptor, raising the question of whether different IFN subtypes possess specific functions. As some confusion existed in the identity and characteristics of mouse IFN-{alpha} subtypes, the availability of data from the mouse genome sequence prompted us to characterize the murine IFN-{alpha} family. A total of 14 IFN-{alpha} genes were detected in the mouse genome, in addition to three IFN-{alpha} pseudogenes. Four IFN-{alpha} genes (IFN-{alpha}1, IFN-{alpha}7/10, IFN-{alpha}8/6, and IFN-{alpha}11) exhibited surprising allelic divergence between 129/Sv and C57BL/6 mice. All IFN-{alpha} subtypes were found to be stable at pH 2 and to exhibit antiviral activity. Interestingly, some IFN subtypes (IFN-{alpha}4, IFN-{alpha}11, IFN-{alpha}12, IFN-ß, and limitin) showed higher biological activity levels than others, whereas IFN-{alpha}7/10 exhibited lower activity. Most murine IFN-{alpha} turned out to be N-glycosylated. However, no correlation was found between N-glycosylation and activity. The various IFN-{alpha} subtypes displayed a good correlation between their antiviral and antiproliferative potencies, suggesting that IFN-{alpha} subtypes did not diverge primarily to acquire specific biological activities but probably evolved to acquire specific expression patterns. In L929 cells, IFN genes activated in response to poly(I•C) transfection or to viral infection were, however, similar.

* Corresponding author. Mailing address: Christian de Duve Institute of Cellular Pathology, University of Louvain, MIPA-VIRO 74-49, 74, avenue Hippocrate, B-1200 Brussels, Belgium. Phone: 32 2 764 74 29. Fax: 32 2 764 74 95. E-mail: michiels{at}mipa.ucl.ac.be.

{dagger} Present address: Laboratoire de Physiologie Animale, IBMM, Université Libre de Bruxelles, B-6041 Gosselies, Belgium

Journal of Virology, August 2004, p. 8219-8228, Vol. 78, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.15.8219-8228.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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