title: Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism.
abstract: The destruction of CD4(+) T cells and eventual induction of immunodeficiency is a hallmark of the human immunodeficiency virus type 1 infection (HIV-1). However, the mechanism of this destruction remains unresolved. Several auxiliary proteins have been proposed to play a role in this aspect of HIV pathogenesis including a 14 kDa protein named viral protein R (Vpr). Vpr has been implicated in the regulation of various cellular functions including apoptosis, cell cycle arrest, differentiation, and immune suppression. However, the mechanism(s) involved in Vpr-mediated apoptosis remains unresolved, and several proposed mechanisms for these effects are under investigation. In this review, we discuss the possibility that some of these proposed pathways might converge to modulate Vpr's behavior. Further, we also discuss caveats and future directions for investigation of the interesting biology of this HIV accessory gene.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: K
authors.initials: K
authors.lastname: Muthumani
authors.forename: A Y
authors.initials: AY
authors.lastname: Choo
authors.forename: A
authors.initials: A
authors.lastname: Premkumar
authors.forename: D S
authors.initials: DS
authors.lastname: Hwang
authors.forename: K P
authors.initials: KP
authors.lastname: Thieu
authors.forename: B M
authors.initials: BM
authors.lastname: Desai
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D000075686:COP9 Signalosome Complex; D002352:Carrier Proteins / Q000502:physiology; D039642:Eukaryotic Initiation Factors / Q000502:physiology; D016336:Gene Products, vpr / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D046912:Multiprotein Complexes / Q000502:physiology; D010447:Peptide Hydrolases / Q000502:physiology; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C470634:COPS6 protein, human; D002352:Carrier Proteins; D039642:Eukaryotic Initiation Factors; D016336:Gene Products, vpr; D018840:HSP70 Heat-Shock Proteins; D046912:Multiprotein Complexes; D011965:Receptors, Glucocorticoid; D054325:vpr Gene Products, Human Immunodeficiency Virus; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex