HIV-1 viral protein R (Vpr) regulates viral replication and cellular proliferation in T cells and monocytoid cells in vitro.
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, which empowers HIV to infect and replicate in non-dividing cells and to increase viral replication, particularly in macrophages. Along with these viral effects, we found that HIV-1 Vpr induces dramatic biological changes in the target cells of HIV infection, including induction of changes in transcriptional patterns, morphological changes, and complete inhibition of proliferation, which collectively was termed differentiation. These changes occur in the absence of other viral gene products, suggesting 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 extended by several groups to demonstrate that the inhibition of proliferation is through G2 cell cycle arrest, further supporting the idea that Vpr acts directly on cellular targets. We have recently described a role for Vpr in modulating the glucocorticoid pathway, which is involved in the regulation of the state of the cell, in cytoplasmic-to-nuclear translocation, and in modulation of host cell transcription. It is important to note that certain anti-glucocorticoid compounds modulate Vpr activity in vitro. These results support the idea that the host cell contains specific receptor molecule(s) through which Vpr mediates its activity. Consequently, 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, USA.
Mahalingam
S
S
Rafaeli
Y
Y
Kudchodkar
S
S
Chang
D
D
Nagashunmugam
T
T
Williams
W V
WV
Weiner
D B
DB
D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D016336:Gene Products, vpr / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000821:virology*; D010446:Peptide Fragments / Q000494:pharmacology; D011533:Proviruses / Q000502:physiology; D015728:Receptors, HIV / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology*; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D005938:Glucocorticoids; D010446:Peptide Fragments; D015728:Receptors, HIV; D054325:vpr Gene Products, Human Immunodeficiency Virus