A human nuclear shuttling protein that interacts with human immunodeficiency virus type 1 matrix is packaged into virions

Active nuclear import of the human immunodeficiency virus type 1 (HIV-1) pr eintegration complex (PIG) is essential for the productive infection of non dividing cells. Nuclear import of the PIC is mediated by the HIV-1 matrix p rotein, which also plays several critical roles during viral entry and poss ibly during virion production facilitating the export of Pr55(Gag) and geno mic RNA. Using a yeast two-hybrid screen, we identified a novel human virio n-associated matrix-interacting protein (VAN) that is highly conserved in v ertebrates and expressed in most human tissues. Its expression is upregulat ed upon activation of CD4(+) T cells. VAN is efficiently incorporated into HIV-1 virions and, like matrix, shuttles between the nucleus and cytoplasm. Furthermore, overexpression of VAN significantly inhibits HIV-1 replicatio n in tissue culture. We propose that VAN regulates matrix nuclear localizat ion and, by extension, both nuclear import of the PIC and export of Pr55(Ga g) and viral genomic RNA during virion production. Our data suggest that th is regulatory mechanism reflects a more global process for regulation of nu cleocytoplasmic transport.