dengue virus serotype 2 blocks extracellular signal-regulated kinase and nuclear factor-κb activation to downregulate cytokine production登革2型病毒阻断细胞外signal-regulated激酶和核factor-κb激活细胞因子表达下调生产.pdfVIP

Dengue Virus Serotype 2 Blocks Extracellular Signal- Regulated Kinase and Nuclear Factor-kB Activation to Downregulate Cytokine Production 1 1 2 1,3 4,5 6 Tsung-Hsien Chang *, Siang-Ru Chen , Chia-Yi Yu , You-Sheng Lin , Yao-Shen Chen , Toru Kubota , 7 2 Mayumi Matsuoka , Yi-Ling Lin * 1 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 2 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, 3 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, 4 Section of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 5 Section of Microbiology, Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 6 Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan, 7 Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan Abstract Background: Dengue virus (DENV) infection is the most common mosquito-borne viral disease threatening human health around the world. Type I interferon (IFN) and cytokine production are crucial in the innate immune system. We previously reported that DENV serotype 2 (DENV-2) induced low levels of interferon regulatory factor 3 and NF-kB activation, thus leading to reduced production of IFN-b in the early phase of infection. Here, we determined whether DENV infection not only hampers type I IFN activation but also cytokine production triggered by Toll-like receptor (TLR) signaling. Methodology/Principal Findings: We used quantitative RT-PCR and found that only lo