HIV-1 viral protein R (Vpr) as a regulator of the target cell.
Among the putative 'accessory genes' of HIV-1, the 96 amino acid virion-associated Vpr gene product has been described to have several novel biological activities. These include cytoplasmic-to-nuclear translocation thus empowering HIV to infect and replicate in nondividing cells and to function to increase viral replication, particularly in monocytes. Along with these viral effects, we describe the dramatic biological changes induced by HIV-1 Vpr in the target cells of HIV infection including induction of changes in transcriptional patterns and complete inhibition of proliferation which collectively is termed differentiation. These changes occur in the absence of other viral gene products and suggest that Vpr mediates its proviral effects partially or perhaps solely through modulation of the state of the target cell rather than directly on the virus. The inhibition of proliferation in T-cell lines has been proposed by several groups to demonstrate that the inhibition of proliferation specifically arrests the cell cycle further supporting the notion that Vpr activity is directed at cellular targets. We have recently described a role for Vpr in modulating the glucocorticoid pathway, a pathway involved in the regulation of the state of the cell in cytoplasmic-to-nuclear translocation and in the modulation of host cell transcription. Importantly, certain antiglucocorticoids have been shown to modulate Vpr activity in vitro. These results demonstrate that the cell contains specific receptor(s) molecule(s) through which Vpr mediates its activity and that these molecules have implications for cell biology in general. These results collectively demonstrate that Vpr represents a unique target for anti-HIV drug development and has significance for HIV-1 disease progression.
Ayyavoo
V
V
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Rafaeli
Y
Y
Nagashunmugam
T
T
Mahalingham
S
S
Phung
M T
MT
Hamam
A
A
Williams
W V
WV
Weiner
D B
DB
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000821:virology*; D018450:Disease Progression; D016336:Gene Products, vpr / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus