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Originally published as JGV in Press, 10.1099/vir.0.004416-0 on March 4, 2009 J Gen Virol 90 (2009), 810-817; DOI 10.1099/vir.0.004416-0

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Increased activity of indoleamine 2,3-dioxygenase in serum from acutely infected dengue patients linked to gamma interferon antiviral function

Aniuska Becerra1,{dagger}, Rajas V. Warke1,{dagger}, Kris Xhaja1, Barbara Evans2, James Evans2, Katherine Martin1, Norma de Bosch3, Alan L. Rothman1 and Irene Bosch1

1 Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
2 University of Massachusetts Medical School Proteomic and Mass Spectrometry Core Facility, 365 Plantation Street, Worcester, MA 01605, USA
3 Banco Municipal de Sangre del Distrito Capital, San Jose, Caracas, Venezuela

Correspondence
Irene Bosch
irene.bosch{at}umassmed.edu

The depletion of L-tryptophan (L-Trp) has been associated with the inhibition of growth of micro-organisms and also has profound effects on T cell proliferation and immune tolerance. The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses the rate-limiting step in the catabolic pathway of L-Trp. Gene expression analysis has shown upregulation of genes involved in L-Trp catabolism in in vitro models of dengue virus (DENV) infection. To understand the role of IDO during DENV infection, we measured IDO activity in sera from control and DENV-infected patients. We found increased IDO activity, lower levels of L-Trp and higher levels of L-kynurenine in sera from DENV-infected patients during the febrile days of the disease compared with patients with other febrile illnesses and healthy donors. Furthermore, we confirmed upregulation of IDO mRNA expression in response to DENV infection in vitro, using a dendritic cell (DC) model of DENV infection. We found that the antiviral effect of gamma interferon (IFN-{gamma}) in DENV-infected DCs 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 that it has a role in the immune response to DENV infections in vivo.

{dagger}These authors contributed equally to this work.







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