Back to Search
Start Over
Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest
- Publication Year :
- 1997
-
Abstract
- The human immunodeficiency virus type 1 (HIV-1) vpr gene encodes a protein which induces arrest of cells in the G2 phase of the cell cycle. Here, we demonstrate that following the arrest of cells in G2, Vpr induces apoptosis in human fibroblasts, T cells, and primary peripheral blood lymphocytes. Analysis of various mutations in the vpr gene revealed that the extent of Vpr-induced G2 arrest correlated with the levels of apoptosis. However, the alleviation of Vpr-induced G2 arrest by treatment with the drug pentoxifylline did not abrogate apoptosis. Together these studies indicate that induction of G2 arrest, but not necessarily continued arrest in G2, was required for Vpr-induced apoptosis to occur. Finally, Vpr-induced G2 arrest has previously been correlated with inactivation of the Cdc2 kinase. Some models of apoptosis have demonstrated a requirement for active Cdc2 kinase for apoptosis to occur. Here we show that accumulation of the hypophosphorylated or active form of the Cdc2 kinase is not required for Vpr-induced apoptosis. These studies indicate that Vpr is capable of inducing apoptosis, and we propose that both the initial arrest of cells and subsequent apoptosis may contribute to CD4 cell depletion in HIV-1 disease.
- Subjects :
- G2 Phase
Cell cycle checkpoint
viruses
Immunology
Human immunodeficiency virus (HIV)
Apoptosis
Biology
medicine.disease_cause
Microbiology
Pentoxifylline
Virology
CDC2 Protein Kinase
medicine
Tumor Cells, Cultured
Animals
Humans
Point Mutation
Lymphocytes
Phosphorylation
Gene
Cells, Cultured
Cyclin-dependent kinase 1
Kinase
Gene Products, vpr
Cell Cycle
virus diseases
vpr Gene Products, Human Immunodeficiency Virus
Cell cycle
biochemical phenomena, metabolism, and nutrition
Cell biology
Insect Science
COS Cells
HIV-1
medicine.drug
Research Article
HeLa Cells
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....75a10513646c2836d5004ff89934c774