Human immunodeficiency virus type 2 (HIV-2), like other lentiviruses, is capable of infecting nondividing T cells and macrophages. The present work shows that in HIV-2-infected cells, Vpx is necessary for efficient nuclear import of the preintegration complex. In agreement with this finding, the subcellular localization of a GFP-Vpx fusion protein was found to be predominantly nuclear. However, deletion of the proline-rich C-terminal 11 residues of Vpx resulted in a shift of the fusion protein to the cytoplasm. Furthermore, the same deletion in the context of the provirus resulted in a decrease in nuclear import of the preintegration complex and attenuated replication in macrophages.

Vpx is a virion-associated protein of human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency viruses. The yeast two-hybrid system was used to identify invariant chain (Ii) as a cellular protein that interacts with HIV-2 Vpx. Vpx-Ii interaction was confirmed in cell-free reactions using bacterially expressed glutathione S-transferase fusion proteins and by coimmunoprecipitation in transfected and infected cells. In chronically infected cells expressing Vpx, Ii levels were markedly decreased, presumably due to enhanced degradation. These findings suggest that Vpx may disrupt major histocompatibility complex class II antigen presentation.

Incorporation of Vpx into human immunodeficiency virus type 2 (HIV-2) virus-like particles is mediated by the Gag polyprotein. We have identified residues 15 to 40 of Gag p6 and residues 73 to 89 of Vpx as being necessary for virion incorporation. In addition, we show enhanced in vitro binding of Vpx to a chimeric HIV-1/HIV-2 Gag construct containing residues 2 to 49 of HIV-2 p6 and demonstrate that the presence of residues 73 to 89 of Vpx allows for in vitro binding to HIV-2 Gag.