title: Biophysical Characterization of Nucleophosmin Interactions with Human Immunodeficiency Virus Rev and Herpes Simplex Virus US11.
abstract: Nucleophosmin (NPM1, also known as B23, numatrin or NO38) is a pentameric RNA-binding protein with RNA and protein chaperon functions. NPM1 has increasingly emerged as a potential cellular factor that directly associates with viral proteins; however, the significance of these interactions in each case is still not clear. In this study, we have investigated the physical interaction of NPM1 with both human immunodeficiency virus type 1 (HIV-1) Rev and Herpes Simplex virus type 1 (HSV-1) US11, two functionally homologous proteins. Both viral proteins show, in mechanistically different modes, high affinity for a binding site on the N-terminal oligomerization domain of NPM1. Rev, additionally, exhibits low-affinity for the central histone-binding domain of NPM1. We also showed that the proapoptotic cyclic peptide CIGB-300 specifically binds to NPM1 oligomerization domain and blocks its association with Rev and US11. Moreover, HIV-1 virus production was significantly reduced in the cells treated with CIGB-300. Results of this study suggest that targeting NPM1 may represent a useful approach for antiviral intervention.
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Kazem
authors.initials: K
authors.lastname: Nouri
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Jens M
authors.initials: JM
authors.lastname: Moll
authors.affiliation: Laboratory of Chemical Biology & Institute of Complex Molecular Systems, Department of Biomedical Engineering, Technische Universiteit Eindhoven, Eindhoven, Netherlands.
authors.forename: Lech-Gustav
authors.initials: LG
authors.lastname: Milroy
authors.affiliation: Clinic for Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Hain
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Radovan
authors.initials: R
authors.lastname: Dvorsky
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Amin
authors.affiliation: Institute of Biochemistry, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lenders
authors.affiliation: Institute of Complex Systems (ICS-6), Research Centre Jülich, Jülich, Germany.|Institute of Physical Biology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Luitgard
authors.initials: L
authors.lastname: Nagel-Steger
authors.affiliation: Institute of Virology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Howe
authors.affiliation: Institute of Biochemistry, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Sander H J
authors.initials: SH
authors.lastname: Smits
authors.affiliation: Institute of Virology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.|Institute of Virology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.affiliation: Institute of Biochemistry, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Schmitt
authors.affiliation: Clinic for Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Münk
authors.affiliation: Laboratory of Chemical Biology & Institute of Complex Molecular Systems, Department of Biomedical Engineering, Technische Universiteit Eindhoven, Eindhoven, Netherlands.
authors.forename: Luc
authors.initials: L
authors.lastname: Brunsveld
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Ahmadian
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D019556:COS Cells; D002522:Chlorocebus aethiops; D015497:HIV-1; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D000090243:Nucleophosmin; D010456:Peptides, Cyclic / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D010456:Peptides, Cyclic; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; D014764:Viral Proteins; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1; D000090243:Nucleophosmin; C532510:CIGB-300