title: Human immunodeficiency virus type 1 vpr induces apoptosis through caspase activation.
abstract: Human immunodeficiency virus type 1 (HIV-1) Vpr is a 96-amino-acid protein that is found associated with the HIV-1 virion. Vpr induces cell cycle arrest at the G(2)/M phase of the cell cycle, and this arrest is followed by apoptosis. We examined the mechanism of Vpr-induced apoptosis and found that HIV-1 Vpr-induced apoptosis requires the activation of a number of cellular cysteinyl aspartate-specific proteases (caspases). We demonstrate that ectopic expression of anti-apoptotic viral proteins, which inhibit caspase activity, and addition of synthetic peptides, which represent caspase cleavage sites, can inhibit Vpr-induced apoptosis. Finally, inhibition of caspase activity and subsequent inhibition of apoptosis results in increased viral expression, suggesting that therapeutic strategies aimed at reducing Vpr-induced apoptosis in vivo require careful consideration.
authors.affiliation: Departments of Microbiology and Immunology and Medicine, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Stewart
authors.forename: B
authors.initials: B
authors.lastname: Poon
authors.forename: J Y
authors.initials: JY
authors.lastname: Song
authors.forename: I S
authors.initials: IS
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D016336:Gene Products, vpr / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus; D020169:Caspases