VIRAL PROTEIN-R REGULATES DOCKING OF THE HIV-1 PREINTEGRATION COMPLEXTO THE NUCLEAR-PORE COMPLEX

Replication of human immunodeficiency virus type 1 (HIV-1) in non-divi ding cells depends critically on import of the viral preintegration co mplex into the nucleus. Recent evidence suggests that viral protein R (Vpr) plays a key regulatory role in this process by binding to karyop herin alpha, a cellular receptor for nuclear localization signals, and increasing its affinity for the nuclear localization signals. An in v itro binding assay was used to investigate the role of Vpr in docking of the HIV-1 preintegration complex (PIC) to the nuclear pore complex. Mutant HIV-1 PICs that lack Vpr were impaired in the ability to dock to isolated nuclei and recombinant nucleoporins. Although Vpr by itsel f associated with nucleoporins, the docking of Vpr(+) PICs was depende nt on karyopherin beta and was blocked by antibodies to beta. Vpr stab ilized docking by preventing nucleoporin-stimulated dissociation of th e import complex. These results suggest a biochemical mechanism for Vp r function in transport of the HIV-1 genome across the nuclear pore co mplex.