title: Nucleolin interacts with the dengue virus capsid protein and plays a role in formation of infectious virus particles.
abstract: Dengue virus (DENV) is a mosquito-transmitted flavivirus that can cause severe disease in humans and is considered a reemerging pathogen of significant importance to public health. The DENV capsid (C) protein functions as a structural component of the infectious virion; however, it may have additional functions in the virus replicative cycle. Here, we show that the DENV C protein interacts and colocalizes with the multifunctional host protein nucleolin (NCL). Furthermore, we demonstrate that this interaction can be disrupted by the addition of an NCL binding aptamer (AS1411). Knockdown of NCL with small interfering RNA (siRNA) or treatment of cells with AS1411 results in a significant reduction of viral titers after DENV infection. Western blotting and quantitative RT-PCR (qRT-PCR) analysis revealed no differences in viral RNA or protein levels at early time points postinfection, suggesting a role for NCL in viral morphogenesis. We support this hypothesis by showing that treatment with AS1411 alters the migration characteristics of the viral capsid, as visualized by native electrophoresis. Here, we identify a critical interaction between DENV C protein and NCL that represents a potential new target for the development of antiviral therapeutics.
authors.affiliation: Cytokine Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Corey A
authors.initials: CA
authors.lastname: Balinsky
authors.forename: Hana
authors.initials: H
authors.lastname: Schmeisser
authors.forename: Sundar
authors.initials: S
authors.lastname: Ganesan
authors.forename: Kavita
authors.initials: K
authors.lastname: Singh
authors.forename: Theodore C
authors.initials: TC
authors.lastname: Pierson
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Zoon
mesh_terms: D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D003715:Dengue / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release; D014779:Virus Replication; D000097796:Nucleolin
chemical_list: D036022:Capsid Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin
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