P&S Journal: Spring 1996, Vol.16, No.2
Researchers Find HIV Gene Blocks Protein Responsible for Cell Growth
Anew study offers fresh insights into how vpr, a gene of the human immunodeficiency virus (HIV), stops cell growth. The study is one of three recent papers that attempt to define the mechanism by which the gene disrupts cell replication.
A team led by Dr. Jeremy Luban, assistant professor of microbiology and of medicine, published its findings in the November issue of the Journal of Virology. The other two studies, also published in the Journal of Virology, were conducted at NYU and UCLA. Columbia researchers found that vpr stops cells from replicating by blocking the process of cell division at a specific stage, just after the cell has copied its DNA but before it has divided. This stage of cell division is known as G2. (Cell division begins with stage GO, the resting stage, which is followed by G1, in which the cell prepares to replicate. At S, the cell synthesizes its DNA and at G2, the cell prepares to divide. The final stage, M, is mitosis, in which the cell divides.) The other two studies reached similar conclusions. The gene appears to stop cell growth by blocking a cascade of reactions that signal a cell to begin mitosis. "We believe that vpr makes the cell think it is not ready to go into mitosis," says Dr. Luban. Vpr accomplishes this by blocking the activation of p34ede2, a cellular protein.
Though the studies have given scientists a better understanding of vpr, the role of the gene in allowing HIV to shut down the immune system and replicate is not clear, says Dr. Luban. "We still don't know why blocking cell division in G2 would be an advantage to HIV." One possible explanation is that vpr stops cell growth in G2 because that stage is important to the HIV virus. For instance, there may be specific transcription factors that are particularly abundant at G2. Or, the G2 stage may protect the cell so that it doesn't die, allowing more HIV to be produced. Finally, it is equally likely that arresting cell growth has no real relevance to the replication of HIV but is simply a secondary effect. More studies are needed to determine the function of vpr, says Dr. Luban.