1. ¹Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA
2. ²Department of Neuroscience and Center for Neurovirology, Temple University School of Medicine, Temple University, Philadelphia, PA, USA
3. ³Unite de Pharmacologie Chimique et Genetique, INSERM, Avenue de l'Observatoire, Paris Cedex 06, France
4. ⁴Department of Cell Biology, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland
5. ⁵Department of Mechanical Engineering, Temple University, Philadelphia, PA, USA
6. ⁶Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

Correspondence: Dr BE Sawaya, Department of Neuroscience and Center for Neurovirology, Temple University School of Medicine, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA. E-mail: sawaya@temple.edu

Received 28 November 2006; Revised 17 May 2007; Accepted 29 May 2007; Published online 23 July 2007.

Abstract

The human immunodeficiency virus type 1 (HIV-1) viral protein R (vpr) gene is an evolutionarily conserved gene among the primate lentiviruses. Several functions are attributed to Vpr including the ability to cause cell death, cell cycle arrest, apoptosis and DNA damage. The Vpr domain responsible for DNA damage as well as the mechanism(s) through which Vpr induces this damage is unknown. Using site-directed mutagenesis, we identified the helical domain II within Vpr (aa 37–50) as the region responsible for causing DNA damage. Interestingly, Vpr (37–50) failed to cause cell cycle arrest or apoptosis, to induce Ku70 or Ku80 and to suppress tumor growth, but maintained its capability to activate the HIV-1 LTR, to localize to the nucleus and to promote nonhomologous end-joining. In addition, our cytogenetic data indicated that helical domain II induced chromosomal aberrations, which mimicked those induced by cisplatin, an anticancer agent. This novel molecular mimicry function of Vpr might lead to its potential therapeutic use as a tumor suppressor.