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Published online ahead of print on 4 March 2009 as doi:10.1099/vir.0.004416-0
Journal of General Virology 2009;90:810.

A more recent version of this article appeared on April 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.004416-0
© 2009 Society for General Microbiology
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Increase activity of Indoleamine 2,3-dioxygenase in serum of acutely infected dengue patients linked to interferon-gamma antiviral function

Aniuska Becerra1, Rajas Warke1, Kris Xhaja1, Barbara Evans1, James Evans1, Katherine J Martin1, Norma de Bosch2, Alan L Rothman1 and Irene Bosch1,3

1 University of Massachusetts Medical School;
2 Banco de Sangre. Caracas

3 E-mail: irene.bosch{at}umassmed.edu

The depletion of L-tryptophan has been associated with the inhibition of growth of microorganisms and also has profound effects on T cell proliferation and immune tolerance. The enzyme Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step in the catabolic pathway of L-tryptophan. Gene expression analysis has shown up-regulation of genes involved in L-tryptophan catabolism in models of dengue virus (DENV)-infection in vitro. To understand the role of IDO during DENV infection, we measured IDO activity in serum from controls and DENV-infected patients. We found increased IDO activity, lower levels of L-tryptophan and higher levels of L-kynurenine, in serum from DENV-infected patients during the febrile days of the disease, as compared to patients with other febrile illnesses and healthy donors. Furthermore, we confirmed up-regulation of IDO mRNA expression in response to DENV in vitro, using a dendritic cell (DC) model of DENV infection. We found that the antiviral effect of IFN-{gamma} in DENV-infected DC in vitro was partially dependent on IDO activity. Our results demonstrate that IDO plays an important role in the antiviral effect of IFN-{gamma} against DENV infection in vitro and suggest a role in the immune response to DENV infections in vivo.

Received 21 June 2008; accepted 7 December 2008.




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