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Clinical and Vaccine Immunology, June 2007, p. 756-766, Vol. 14, No. 6
1071-412X/07/$08.00+0     doi:10.1128/CVI.00052-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Transcriptional Activation of Interferon-Stimulated Genes but Not of Cytokine Genes after Primary Infection of Rhesus Macaques with Dengue Virus Type 1{triangledown}

Carlos A. Sariol,1,2,3* Jorge L. Muñoz-Jordán,4 Kristina Abel,5 Lymarie C. Rosado,2 Petraleigh Pantoja,1 Luis Giavedoni,6 Idia Vanessa Rodriguez,1 Laura J. White,7 Melween Martínez,1 Teresa Arana,2 and Edmundo N. Kraiselburd1,2

Unit of Comparative Medicine, Caribbean Primate Research Center,1 Department of Microbiology and Medical Zoology,2 Department of Internal Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico,3 Molecular Virology and Surveillance Laboratory, Center for Disease Control, Dengue Branch, San Juan, Puerto Rico,4 California National Primate Research Center, University of California, Davis, Davis, California,5 Department of Virology and Immunology, Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, Texas,6 Carolina Vaccine Institute, University of North Carolina, Chapel Hill, North Carolina7

Received 12 January 2007/ Returned for modification 25 February 2007/ Accepted 12 March 2007

Macaques are the only animal model used to test dengue virus (DENV) vaccine candidates. Nevertheless, the pathogenesis of DENV in macaques is not well understood. In this work, by using Affymetrix oligonucleotide microarrays, we studied the broad transcriptional modifications and cytokine expression profile after infecting rhesus macaques with DENV serotype 1. Five days after infection, these animals produced a potent, innate antiviral immune response by inducing the transcription of signature genes from the interferon (IFN) pathway with demonstrated antiviral activity, such as myxoprotein, 2',5'-oligoadenylate synthetase, phospholipid scramblase 1, and viperin. Also, IFN regulatory element 7, IFN-stimulated gene 15, and protein ligases linked to the ISGylation process were up-regulated. Unexpectedly, no up-regulation of IFN-{alpha}, -ß, or -{gamma} genes was detected. Transcription of the genes of interleukin-10 (IL-10), IL-8, IL-6, and tumor necrosis factor alpha was neither up-regulated nor down-regulated. Results were confirmed by real-time PCR and by multiplex cytokine detection in serum samples.

* Corresponding author. Mailing address: Department of Microbiology, University of Puerto Rico, Main Building, 3rd Floor, Office B-315, School of Medicine, Medical Sciences Campus, P.O. Box 365067, Rio Piedras, San Juan, PR 00936-5067. Phone: (787) 758-2525, ext. 5112. Fax: (787) 767-1442. E-mail: csariol{at}rcm.upr.edu

{triangledown} Published ahead of print on 11 April 2007.

Clinical and Vaccine Immunology, June 2007, p. 756-766, Vol. 14, No. 6
1071-412X/07/$08.00+0     doi:10.1128/CVI.00052-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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