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Journal of Virology, June 2005, p. 7768-7776, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7768-7776.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Indoleamine 2,3-Dioxygenase Mediates Cell Type-Specific Anti-Measles Virus Activity of Gamma Interferon

Karola Obojes,1 Oliver Andres,1 Kwang Sik Kim,2 Walter Däubener,3 and Jürgen Schneider-Schaulies1*

Institut für Virologie und Immunbiologie, Julius-Maximilians-Universität, 97078 Würzburg, Germany,1 Johns Hopkins University School of Medicine, Baltimore, Maryland 21287,2 Institut für Medizinische Mikrobiologie, Heinrich-Heine-Universität, 40225 Düsseldorf, Germany3

Received 19 July 2004/ Accepted 26 January 2005

Gamma interferon (IFN-{gamma}) has been shown to be increased in sera from patients with acute measles and after vaccination, to exhibit protective functions in brains of patients with subacute sclerosing panencephalitis, and to mediate a noncytolytic clearance of measles virus (MV) from rodent brains. In order to reveal a possible intracellular antiviral activity in the absence of antigen presentation and cytotoxic T cells, we investigated IFN-{gamma}-induced effects on MV replication in various tissue culture cells. While attenuated MV strains are more sensitive to IFN-{alpha}/ß than are wild-type strains, IFN-{gamma} inhibits the replication of all MV strains in epithelial, endothelial, and astroglial cells, but not in lymphoid and neuronal cell lines. The antiviral activity induced by IFN-{gamma} correlates with the induction of indoleamine 2,3-dioxygenase (IDO), an enzyme of the tryptophan degradation pathway known to mediate antiviral as well as antibacterial and antiparasitic effects. The IFN-{gamma}-induced antiviral activity can be overcome by the addition of excess amounts of L-tryptophan, which indicates a specific role of IDO in the anti-MV activity. Our data suggest that the IFN-{gamma}-induced enzyme IDO plays an important antiviral role in MV infections of epithelial, endothelial, and astroglial cells.

* Corresponding author. Mailing address: Institut für Virologie und Immunbiologie, Versbacher Str. 7, D-97078 Würzburg, Germany. Phone: 49-931-20149895. Fax: 49-931-20149553. E-mail: jss{at}vim.uni-wuerzburg.de.

Journal of Virology, June 2005, p. 7768-7776, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7768-7776.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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