Comparison of cell cycle arrest, transactivation, and apoptosis induced by the simian immunodeficiency virus SIVagm and human immunodeficiency virus type 1 vpr genes.
All primate lentiviruses known to date contain one or two open reading frames with homology to the human immunodeficiency virus type 1 (HIV-1) vpr gene. HIV-1 vpr encodes a 96-amino-acid protein with multiple functions in the viral life cycle. These functions include modulation of the viral replication kinetics, transactivation of the long terminal repeat, participation in the nuclear import of preintegration complexes, induction of G2 arrest, and induction of apoptosis. The simian immunodeficiency virus (SIV) that infects African green monkeys (SIVagm) contains a vpr homologue, which encodes a 118-amino-acid protein. SIVagm vpr is structurally and functionally related to HIV-1 vpr. The present study focuses on how three specific functions (transactivation, induction of G2 arrest, and induction of apoptosis) are related to one another at a functional level, for HIV-1 and SIVagm vpr. While our study supports previous reports demonstrating a causal relationship between induction of G2 arrest and transactivation for HIV-1 vpr, we demonstrate that the same is not true for SIVagm vpr. Transactivation by SIVagm vpr is independent of cell cycle perturbation. In addition, we show that induction of G2 arrest is necessary for the induction of apoptosis by HIV-1 vpr but that the induction of apoptosis by SIVagm vpr is cell cycle independent. Finally, while SIVagm vpr retains its transactivation function in human cells, it is unable to induce G2 arrest or apoptosis in such cells, suggesting that the cytopathic effects of SIVagm vpr are species specific. Taken together, our results suggest that while the multiple functions of vpr are conserved between HIV-1 and SIVagm, the mechanisms leading to the execution of such functions are divergent.
Department of Medicine, University of Rochester Cancer Center, Rochester, New York 14642, USA.
Y
Y
Zhu
H A
HA
Gelbard
M
M
Roshal
S
S
Pursell
B D
BD
Jamieson
V
V
Planelles
D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019556:COS Cells; D002110:Caffeine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002522:Chlorocebus aethiops; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D016334:Genes, vpr / Q000235:genetics; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D008954:Models, Biological; D017239:Paclitaxel / Q000494:pharmacology; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus; D002110:Caffeine; D017239:Paclitaxel