Autor(es): 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, Tan Yee-Joo, Sawasaki Tatsuya, Chu Justin Jang Hann, Vasudevan Subhash G, Sano Kouichi, Yamamoto Naoki

Resumo: 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 - 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 - 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, - 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), - La motif-related protein 1 (LARP1). Interestingly, PABPC1 - LARP1 were found to be positive modulators of DENV replication. Since RyDEN influenced intracellular events on DENV replication -, 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 - cellular mRNA-binding proteins, resulting in the inhibition of virus replication in infected cells.

Imprenta: PLoS Pathogens, v. 12, n. 1, p. e1005357, 2016

Identificador do objeto digital: 10.1371/journal.ppat.1005357

Descritores: Chikungunya virus - Cell ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Protein synthesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Immune response ; Chikungunya virus - Infectious diseases ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Dengue

Data de publicação: 2016

INDICADORES

ACESSO