title: Eukaryotic initiation factor 4AI interacts with NS4A of Dengue virus and plays an antiviral role.
abstract: Dengue virus (DENV) is a mosquito-borne flavivirus that causes the most prevalent diseases in tropical and subtropical regions. DENV utilizes host factors to facilitate its replication, while host cells intend to restrain virus replication. NS4A of DENV has been implicated to play a crucial role during viral replication. To identify more cellular proteins that are recruited by NS4A, we carried out a tandem affinity purification assay. The mass spectrometry data revealed that human eukaryotic initiation factor 4AI (eIF4AI) was one of potential NS4A-interacting partners. Co-immunoprecipitation data confirmed the interaction between NS4A and eIF4AI, and both the N-terminal ATP-binding domain and C-terminal helicase domain of eIF4AI were involved in their association. Functionally, silencing of eIF4AI by RNAi significantly increased the replication level of DENV1, DENV2 and DENV3. And knockdown of eIF4AI markedly attenuated the phosphorylation of protein kinase regulated by dsRNA-activated (PKR) and eIF2ɑ induced by DENV2 infection. Collectively, these data suggested that a potential role of NS4A in antagonizing host antiviral defense is by recruiting eIF4AI and escaping the translation inhibition mediated by PKR.
authors: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510623, China.
authors: Xiaoyan
authors: X
authors: Chen
authors: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510623, China.
authors: Jun
authors: J
authors: Xia
authors: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510623, China.
authors: Qirui
authors: Q
authors: Zhao
authors: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510623, China.
authors: Yi
authors: Y
authors: Wang
authors: Guangdong Inspection and Quarantine Technology Center, Guangzhou 510080, China.
authors: Jingyu
authors: J
authors: Liu
authors: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510623, China.
authors: Lianqiang
authors: L
authors: Feng
authors: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510623, China. Electronic address: hejf@mail.sysu.edu.cn.
authors: Junfang
authors: J
authors: He
authors: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510623, China. Electronic address: zhangp36@mail.sysu.edu.cn.
authors: Ping
authors: P
authors: Zhang
mesh_terms: D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003716:Dengue Virus / Q000502:physiology*; D039601:Eukaryotic Initiation Factor-4A / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000821:virology*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014775:Virus Activation / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D017361:Viral Nonstructural Proteins; D039601:Eukaryotic Initiation Factor-4A
keywords: Dengue virus; NS4A; PKR; eIF4AI