S. Popov et al., VIRAL PROTEIN-R REGULATES DOCKING OF THE HIV-1 PREINTEGRATION COMPLEXTO THE NUCLEAR-PORE COMPLEX, The Journal of biological chemistry, 273(21), 1998, pp. 13347-13352
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.