Kazem Nouri 1 , Jens M. Moll 1 , Lech-Gustav Milroy 2 , Anika Hain 3 , Radovan Dvorsky 1 , Ehsan Amin 1 , Michael Lenders 4 , Luitgard Nagel-Steger 5 , 6 , Sebastian Howe 7 , Sander H. J. Smits 4 , Hartmut Hengel 7 , 8 , Lutz Schmitt 4 , Carsten Münk 3 , Luc Brunsveld 2 , Mohammad R. Ahmadian 1 , *
1 December 2015
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.