host gene expression profiling of dengue virus infection in cell lines and patients登革病毒感染宿主基因表达分析在细胞系和病人.pdfVIP

Host Gene Expression Profiling of Dengue Virus Infection in Cell Lines and Patients 1. 1. 2 2 2 2 Joshua Fink , Feng Gu , Ling Ling , Thomas Tolfvenstam , Farzad Olfat , Keh Chuang Chin , Pauline 2 2 2 1 1 Aw , Joshy George , Vladimir A. Kuznetsov , Mark Schreiber , Subhash G. Vasudevan *, Martin L. Hibberd2 1 Novartis Institute for Tropical Diseases, Chromos, Singapore, 2 Genome Institute of Singapore, Genome, Singapore Abstract Background: Despite the seriousness of dengue-related disease, with an estimated 50–100 million cases of dengue fever and 250,000–500,000 cases of dengue hemorrhagic fever/dengue shock syndrome each year, a clear understanding of dengue pathogenesis remains elusive. Because of the lack of a disease model in animals and the complex immune interaction in dengue infection, the study of host response and immunopathogenesis is difficult. The development of genomics technology, microarray and high throughput quantitative PCR have allowed researchers to study gene expression changes on a much broader scale. We therefore used this approach to investigate the host response in dengue virus- infected cell lines and in patients developing dengue fever. Methodology/Principal Findings: Using microarray and high throughput quantitative PCR method to monitor the host response to dengue viral replication in cell line infection models and in dengue patient blood samples, we identified differentially expressed genes along three major pathways; NF-kB initiated immune responses, type I interferon (IFN) and the