Background:  Vpr plays an important role in transport of the viral pre-integration complex into the nucleus.  Consistent with this role, Vpr contains nuclear localization signals and has also recently been shown to be involved in cytoplasmic-nuclear shuffling. 

Methods:  We have made a number of observations about the dynamics of Vpr localization and its relationship with the nucleus in the fission yeast model system. 

Results:  First, Vpr localizes predominantly on the nuclear envelope and accumulates at the nuclear pores and possibly at the spindle pole bodies during mitosis. Using a live cell analysis of Vpr fused to GFP, we have found that blebbing of the nuclear envelope sometimes occurs indicating that Vpr can cause large distortions in the nuclear envelope.  Second, the localization of Vpr on the nuclear envelope can be dramatically affected by the overexpression of other genes.  One of the genes affecting localization of Vpr is UNG, a gene encoding uracil DNA glycosylase which binds to Vpr and is specifically recruited into the viral particles. Overexpression of human UNG can target much of the Vpr either into the nucleus or to the mitochondria depending on which form of human UNG is overexpressed.  In contrast, overexpression of a mammalian HSP70 gene targets Vpr to a single spot on the nuclear envelope, which may be the spindle pole body.  Another gene affecting localization of Vpr is rad25, a homologue of human 14-3-3 genes, which when overexpressed leads to localization of Vpr in the cytoplasm.  Normally, 14-3-3 homologues bind to phosphorylated Cdc25 upon induction of the checkpoint and shuffle it into the cytoplasm resulting in G2 arrest. Interestingly, Vpr also affect the cellular localization of Cdc25 as expression of Vpr moves most of Cdc25 to the cytoplasm.  This exclusion of the cell cycle regulator Cdc25 from the nucleus may partly explain the induction of cell cycle G2 arrest by Vpr. 

Conclusions:  Together, these altered localizations for Vpr after overexpression of other genes suggest that the localization of Vpr may vary depending upon the cellular proteins it associates with and these changes in cellular distribution may be essential to the multiple roles of Vpr during HIV-1 infection.