Gene Expression in Human Macrophages Infected with Dengue Virus Serotype-2

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Abstract
Infection by any of the four serotypes of dengue viruses (DEN-1, -2, -3 and -4) may result in either a relatively benign fever, called dengue fever (DF), a fatal disease, such as dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS). Several lines of evidence suggest that soluble immune response mediators may be involved in the severity of dengue infections. For instance, elevated seric levels of IL-8 are a common feature in DHF patients. Because other chemokines, cytokines, adhesion molecules, chemokine and cytokine receptors, as well as cytokine-related molecules may also be involved in dengue virus pathogenesis, we aimed at analysing the gene expression of such molecules in the course of an in vitro DEN-2 infection of human peripheral blood monocyte-derived macrophages, a cell type regarded as a primary target for DEN. Nylon membrane gene arrays containing 375 different human cytokine-related genes were used as a first step to search for differentially expressed genes upon infection. Transcripts for IL-8, IL-1beta, osteopontin, GRO-alpha, -beta and -gamma, I-309, and some other molecules showed to be upregulated upon infection, whereas others such as MIC-1, CD27L and CD30L, were downregulated. Four genes were selected for reverse transcriptase-polymerase chain reaction based gene-expression analysis as a way to partially confirm microarray results. This approach pointed out 25 macrophage-expressed cytokine-related genes that could be relevant in DEN-2 pathogenesis.