Transcriptional activation of interferon-stimulated genes but not of cytokine genes after primary infection of rhesus macaques with dengue virus type 1.
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, -beta, 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.
Sariol
Carlos A
CA
Unit of Comparative Medicine, Primate Research Center, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936-5067. csariol@rcm.upr.edu
Muñoz-Jordán
Jorge L
JL
Abel
Kristina
K
Rosado
Lymarie C
LC
Pantoja
Petraleigh
P
Giavedoni
Luis
L
Rodriguez
Idia Vanessa
IV
White
Laura J
LJ
Martínez
Melween
M
Arana
Teresa
T
Kraiselburd
Edmundo N
EN
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000145:classification / Q000472:pathogenicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate; D007372:Interferons / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012703:Serotyping; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D016207:Cytokines; D011506:Proteins; D007372:Interferons