title: Additive Promotion of Viral Internal Ribosome Entry Site-Mediated Translation by Far Upstream Element-Binding Protein 1 and an Enterovirus 71-Induced Cleavage Product.
abstract: The 5' untranslated region (5' UTR) of the enterovirus 71 (EV71) RNA genome contains an internal ribosome entry site (IRES) that is indispensable for viral protein translation. Due to the limited coding capacity of their RNA genomes, EV71 and other picornaviruses typically recruit host factors, known as IRES trans-acting factors (ITAFs), to mediate IRES-dependent translation. Here, we show that EV71 viral proteinase 2A is capable of cleaving far upstream element-binding protein 1 (FBP1), a positive ITAF that directly binds to the EV71 5' UTR linker region to promote viral IRES-driven translation. The cleavage occurs at the Gly-371 residue of FBP1 during the EV71 infection process, and this generates a functional cleavage product, FBP11-371. Interestingly, the cleavage product acts to promote viral IRES activity. Footprinting analysis and gel mobility shift assay results showed that FBP11-371 similarly binds to the EV71 5' UTR linker region, but at a different site from full-length FBP1; moreover, FBP1 and FBP11-371 were found to act additively to promote IRES-mediated translation and virus yield. Our findings expand the current understanding of virus-host interactions with regard to viral recruitment and modulation of ITAFs, and provide new insights into translational control during viral infection.
authors: Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.|Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
authors: Chuan-Tien
authors: CT
authors: Hung
authors: Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.|Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
authors: Yu-An
authors: YA
authors: Kung
authors: Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, New Jersey, United States Of America.
authors: Mei-Ling
authors: ML
authors: Li
authors: Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, New Jersey, United States Of America.
authors: Gary
authors: http://orcid.org/0000-0002-4180-3964
authors: G
authors: Brewer
authors: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
authors: Kuo-Ming
authors: KM
authors: Lee
authors: Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.|Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
authors: Shih-Tung
authors: ST
authors: Liu
authors: Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.|Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.|Clinical Virology Laboratory, Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan City, Taiwan.
authors: Shin-Ru
authors: SR
authors: Shih
mesh_terms: D020121:5' Untranslated Regions / Q000502:physiology; D045744:Cell Line, Tumor; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D029821:Enterovirus A, Human; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D000067556:Internal Ribosome Entry Sites / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology; D016601:RNA-Binding Proteins; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; D000067556:Internal Ribosome Entry Sites; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D004265:DNA Helicases