Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr-independent HIV-1 replication in macrophages.

HIV-1 viral protein R (Vpr) shuttles between the nucleus and the cytoplasm and is believed to contribute to the process of nuclear translocation of the viral preintegration complex, thus facilitating HIV-1 replication in macrophages. In this report, we demonstrate that Hsp70, a heat-shock protein contributing to cellular stress responses, inhibits nuclear translocation of HIV-1 Vpr. In macrophages, Hsp70 is induced shortly after HIV-1 infection.

Phosphorylation of Vpr regulates HIV type 1 nuclear import and macrophage infection.

Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) is a small accessory protein that regulates nuclear import of the viral preintegration complex and facilitates infection of nondividing cells, such as macrophages. Studies demonstrated that a fraction of Vpr molecules is phosphorylated in the virions and in HIV-1-infected cells, but the role of phosphorylation in nuclear import activity of Vpr has not been established. We found that Vpr is phosphorylated predominantly on the serine residue in position 79, and mutations affecting Vpr phosphorylation significantly attenuated viral replication in macrophages, but not in activated T lymphocytes or cell lines.