Biophysical Characterization of Nucleophosmin Interactions with Human Immunodeficiency Virus Rev and Herpes Simplex Virus US11

PLoS One. 2015 Dec 1;10(12):e0143634. doi: 10.1371/journal.pone.0143634. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysical Phenomena*
  • COS Cells
  • Chlorocebus aethiops
  • HIV-1
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Nucleophosmin
  • Peptides, Cyclic / metabolism
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Quaternary
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism*
  • rev Gene Products, Human Immunodeficiency Virus / chemistry
  • rev Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • NPM1 protein, human
  • Nuclear Proteins
  • Peptides, Cyclic
  • RNA-Binding Proteins
  • US11 protein, herpesvirus
  • Viral Proteins
  • rev Gene Products, Human Immunodeficiency Virus
  • rev protein, Human Immunodeficiency Virus-1
  • Nucleophosmin
  • CIGB-300

Grants and funding

This work was funded by the International Graduate School of Protein Science and Technology (iGRASP), Research Commission of the Medical Faculty and the Strategic Research Fund (SFF) of Heinrich-Heine University Düsseldorf, and the German Research Foundation (Deutsche Forschungsgemeinschaft or DFG) through the Collaborative Research Center 974 (SFB 974) “Communication and Systems Relevance during Liver Injury and Regeneration”, the International Research Training Group 1902 (IRTG 1902) “Intra- and interorgan communication of the cardiovascular system”, and GRK 1045 “Modulation of host cell function”. CM is supported by the Heinz Ansmann foundation. AH is supported by the Jürgen Manchot Foundation, Molecules of Infection Graduate School.