Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism

K Muthumani; A Y Choo; A Premkumar; D S Hwang; K P Thieu; B M Desai; D B Weiner

doi:10.1038/sj.cdd.4401583

Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism

Cell Death Differ. 2005 Aug:12 Suppl 1:962-70. doi: 10.1038/sj.cdd.4401583.

Authors

K Muthumani¹, A Y Choo, A Premkumar, D S Hwang, K P Thieu, B M Desai, D B Weiner

Affiliation

¹ Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

PMID: 15832179
DOI: 10.1038/sj.cdd.4401583

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Apoptosis*
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
CD4-Positive T-Lymphocytes / virology*
COP9 Signalosome Complex
Carrier Proteins / physiology
Eukaryotic Initiation Factors / physiology
Gene Products, vpr / antagonists & inhibitors
Gene Products, vpr / pharmacology
Gene Products, vpr / physiology*
HIV-1 / physiology*
HSP70 Heat-Shock Proteins / pharmacology
Humans
Intracellular Membranes / drug effects
Membrane Potentials / drug effects
Mitochondria / drug effects
Multiprotein Complexes / physiology
Peptide Hydrolases / physiology
Receptors, Glucocorticoid / drug effects
Signal Transduction / drug effects
vpr Gene Products, Human Immunodeficiency Virus

Substances

Adaptor Proteins, Signal Transducing
COPS6 protein, human
Carrier Proteins
Eukaryotic Initiation Factors
Gene Products, vpr
HSP70 Heat-Shock Proteins
Multiprotein Complexes
Receptors, Glucocorticoid
vpr Gene Products, Human Immunodeficiency Virus
Peptide Hydrolases
COP9 Signalosome Complex