Pathology

E-mail: vicente.planelles@path.utah.edu
Address: EEJ Rm 2100
Phone: 581-8655

Vpr in the pathogenesis of primate lentiviruses

The focus of our research is to understand the pathogenesis by primate lentiviruses. We investigate the mechanisms by which primate lentiviruses induce cell cycle disruption and apoptosis in the infected cells. Our results indicate that both arrest and apoptosis are effected via a signaling pathway that is independent of the tumor suppressors, p53 and Rb. Comparisons among vpr-related genes of various primate lentiviruses have shown that the functions of vpr are highly conserved in otherwise divergent strains of the human (HIV) and simian (SIV) immunodeficiency viruses.

We and others have recently discovered that Vpr exerts its functions through manipulation of a ubiquitin ligase composed of cullin 4, the adaptor protein DDB1, the substrate specificity module DCAF1, and the RING domain protein ROC.  Current projects in progress, available for prospective trainees, include (1) the characterization of the Vpr/DCAF1 binding interface; (2) characterization of the three dimensional structure of the complex; (3) determination of the effect of Vpr on the ubiquitin ligase activity of the complex; and (4) identification of the cellular target(s) for this ubiquitin ligase, both in the presence and in the absence of Vpr

1/2008