Human Immunodeficiency Virus Type 1 (HIV-1) Viral Protein R (Vpr)-Mediated Cell Cycle Arrest: An Analysis of Current Mechanistic Models
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD F EDWARD HEBERT SCHOOL OF MEDICINE
Pagination or Media Count:
Human immunodeficiency virus type I HIV-1 infection causes acquired immunodeficiency syndrome AIDS, the most globally devastating viral disease of the past 25 years. Development of effective HIV-1 preventative and therapeutic regimens have proven exceedingly difficult, as the virus has evolved sophisticated mechanisms for thwarting control efforts. A detailed understanding of HIV-1 molecular biology is therefore necessary in order to generate the effective and inexpensive prevention and treatment strategies required for AIDS pandemic curtailment. HIV-1 optimizes its transmissibility and propagation through continual change and coordination of its components functions and life cycle processes with one another and with those of cellular components and processes. Comprehending the molecular bases for HIV-1s abilities to manipulate host cell components and processes is key to the identification of the viruss vulnerabilities. This thesis focuses on one identified effect, G2M cell cycle arrest induction 1-5, of one highly conserved HIV-1 component, viral protein R Vpr 6, 7. A mechanistic understanding of this function is important because arrest at this cell cycle stage provides a selective advantage for the virus transcription from the viral promoter more active during G2, allowing for increased viral replication 8- 14. Other reasons for the selective advantage of G2M arrest, e.g. prevention or delay of cell death by mitotic catastrophe or apoptosis, are also possible 3, 15-23. Covering scientific publications through November 2005, this thesis explores the state of knowledge of the mechanisms underlying Vprs ability to induce G2M cell cycle arrest. The authors goal is to provide a disinterested analysis of the available mechanistic models and their supporting data with the hope of being helpful to the reader in some manner.
- Medicine and Medical Research