Characterization of RyDEN (C19orf66) as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication

• DOI: 10.1371/journal.ppat.1005357
• Publication Date: 2016-01-06T18:36:16Z
• Authors: Youichi Suzuki; Wei-Xin Chin; Qi'En Han; Koji Ichiyama; Ching Hua Lee; Zhi Wen Eyo; Hirotaka Ebina; Hirotaka Takahashi; Chikako Takahashi; Beng Hui Tan; Takayuki Hishiki; Kenji Ohba; Toshifumi Matsuyama; Yoshio Koyanagi; Yee-Joo Tan; Tatsuya Sawasaki; Justin Jang Hann Chu; Subhash G. Vasudevan; Kouichi Sano; Naoki Yamamoto
• Keywords: 0301 basic medicine; 570; QH301-705.5; Immunoblotting; 610; RC581-607; Dengue Virus; Transfection; Virus Replication; Polymerase Chain Reaction; Mass Spectrometry; Cell Line; 3. Good health; Dengue; Viral Proteins; 03 medical and health sciences; Gene Knockdown Techniques; Humans; Immunoprecipitation; Interferons; Immunologic diseases. Allergy; Biology (General); Research Article

Dengue virus (DENV) is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. However, no vaccine or specific antiviral available for dengue. As seen other RNA viruses, innate immune system plays a key role controlling DENV infection and disease outcome. Although interferon (IFN) response, which central to host protective immunity, has been reported limit replication, molecular details how modulated by IFN treatment are elusive. In this study, employing gain-of-function screen using type I IFN-treated cell-derived cDNA library, we identified previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG) inhibits named Repressor yield (RyDEN). Overexpression knockdown experiments revealed expression RyDEN confers resistance all serotypes human cells. also limited replication hepatitis C virus, Kunjin Chikungunya herpes simplex 1, adenovirus. Importantly, was considered be crucial effector molecule IFN-mediated anti-DENV response. When affinity purification-mass spectrometry analysis performed, form complex with cellular mRNA-binding proteins, poly(A)-binding protein cytoplasmic 1 (PABPC1), La motif-related (LARP1). Interestingly, PABPC1 LARP1 were found positive modulators replication. Since influenced intracellular events on and, suppression synthesis from DENV-based reporter construct observed RyDEN-expressing cells, our data suggest likely interfere translation via interaction viral resulting inhibition infected