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Title: Characterization of RyDEN (C19orf66) as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication
Authors: Suzuki, Youichi
Chin, Wei Xin
Han, Qi'En
Ichiyama, Koji
Lee, Ching Hua
Eyo, Zhi Wen
Ebina, Hirotaka
Takahashi, Hirotaka
Takahashi, Chikako
Tan, Beng Hui
Hishiki, Takayuki
Ohba, Kenji
Matsuyama, Toshifumi
Koyanagi, Yoshio  kyouindb  KAKEN_id
Tan, Yee Joo
Sawasaki, Tatsuya
Chu, Justin Jang Hann
Vasudevan, Subhash G.
Sano, Kouichi
Yamamoto, Naoki
Author's alias: 蝦名, 博貴
小柳, 義夫
Issue Date: 6-Jan-2016
Publisher: Public Library of Science
Journal title: PLOS Pathogens
Volume: 12
Issue: 1
Thesis number: e1005357
Abstract: 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 is available for dengue. As seen in other RNA viruses, the innate immune system plays a key role in controlling DENV infection and disease outcome. Although the interferon (IFN) response, which is central to host protective immunity, has been reported to limit DENV replication, the molecular details of how DENV infection is modulated by IFN treatment are elusive. In this study, by employing a gain-of-function screen using a type I IFN-treated cell-derived cDNA library, we identified a previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG) that inhibits DENV replication, which we named Repressor of yield of DENV (RyDEN). Overexpression and gene knockdown experiments revealed that expression of RyDEN confers resistance to all serotypes of DENV in human cells. RyDEN expression also limited the replication of hepatitis C virus, Kunjin virus, Chikungunya virus, herpes simplex virus type 1, and human adenovirus. Importantly, RyDEN was considered to be a crucial effector molecule in the IFN-mediated anti-DENV response. When affinity purification-mass spectrometry analysis was performed, RyDEN was revealed to form a complex with cellular mRNA-binding proteins, poly(A)-binding protein cytoplasmic 1 (PABPC1), and La motif-related protein 1 (LARP1). Interestingly, PABPC1 and LARP1 were found to be positive modulators of DENV replication. Since RyDEN influenced intracellular events on DENV replication and, suppression of protein synthesis from DENV-based reporter construct RNA was also observed in RyDEN-expressing cells, our data suggest that RyDEN is likely to interfere with the translation of DENV via interaction with viral RNA and cellular mRNA-binding proteins, resulting in the inhibition of virus replication in infected cells.
Rights: © 2016 Suzuki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
DOI(Published Version): 10.1371/journal.ppat.1005357
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