HIV and Apoptosis: Death and the Mitochondrion

While a main feature of HIV-1 pathogenesis is the death of CD4⁺ T cells due to apoptosis, the mechanisms of apoptosis are highly controversial 1,2. Several HIV-1 proteins have been implicated in apoptosis regulation, among them viral protein R (Vpr), a small (∼14 kD) HIV-1 accessory protein that is packed in the nucleocapsid through its interaction with the Pr55 Gag precursor 3. In addition to its roles in apoptosis and virus assembly, several other activities have been ascribed to Vpr–protein interaction, including: (a) translocation of the HIV-1 preintegration complex through the nuclear pore, a necessary step for the replication of HIV-1 in nondividing cells—Vpr appears to participate in this process by binding to kariopherin α; (b) induction of cell cycle arrest, likely by Vpr binding to and inactivating MOV34, an upstream positive regulator of...