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Gene expression profiling of dengue infected human primary cells identifies secreted mediators in vivo
Author(s) -
Becerra Aniuska,
Warke Rajas V.,
Martin Katherine,
Xhaja Kris,
de Bosch Norma,
Rothman Alan L.,
Bosch Irene
Publication year - 2009
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.21538
Subject(s) - cxcl10 , dengue virus , biology , dengue fever , chemokine , immunology , tumor necrosis factor alpha , monocyte , immune system , virology , interferon , gene expression profiling , gene expression , gene , biochemistry
We used gene expression profiling of human primary cells infected in vitro with dengue virus (DENV) as a tool to identify secreted mediators induced in response to the infection. Affymetrix GeneChip analysis of human primary monocytes, B cells and dendritic cells infected with DENV in vitro showed strong induction of monocyte chemotactic protein 2 (MCP‐2/CCL8), interferon gamma‐induced protein 10 (IP‐10/CXCL10) and tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL/TNFSF10). The expression of these genes was confirmed in dendritic cells infected with DENV in vitro at mRNA and protein levels. A prospectively enrolled cohort of DENV‐infected Venezuelan patients was used to measure the levels of these proteins in serum during three different periods of the disease. Results showed significant increase of MCP‐2, IP‐10, and TRAIL levels in patients infected with DENV during the febrile period, when compared to healthy donors and patients with other febrile illnesses. MCP‐2 and IP‐10 levels were still elevated during the post‐febrile period while TRAIL levels dropped close to normal after defervescense. Patients with primary infections had higher TRAIL levels than patients with secondary infections during the febrile period of the disease. Increased levels of IP‐10, TRAIL and MCP‐2 in acute DENV infections suggest a role for these mediators in the immune response to the infection. MCP‐2 was identified in this work as a new unreported and important dengue‐related protein and IP‐10 was confirmed as a novel and strong pro‐inflammatory marker in acute disease. J. Med. Virol. 81:1403–1411, 2009. © 2009 Wiley‐Liss, Inc.