AIDS researchers have identified a master chemical switch inside the acquired immune deficiency syndrome virus that is the key element in controlling whether the virus remains dormant in the cell or spreads rapidly among the body's cells.
The latest advance, reported from the laboratory of William A. Haseltine at the Dana Farber Cancer Institute in Boston, identifies the mechanism responsible for the deadly fast-multiplication phase of the virus' life inside the human body, and the location of that mechanism within the cell.
The work gives researchers an important target in searching for drugs to halt AIDS.
The deciphering of this chemical machinery in the AIDS virus has been carried out chiefly by two groups, one directed by Haseltine at Dana Farber, and the other by Flossie Wong-Staal at the National Cancer Institute. The two groups jointly published the first reports of the existence of the chemical switch in the AIDS virus.
In this week's edition of the British journal Nature, Craig A. Rosen and Joseph G. Sodroski of the Haseltine group reported that the gene found in the AIDS virus -- called "TAT" for transactivation and transcription activation -- can adjust its own production, increasing 500 to 1,000 times.
The mechanism, the report said, also may be important in other uses because the amplifying power of the gene remains when it is transplanted to other cells. One of the key problems for biotechnology companies is to coax cells to produce abnormally large amounts of a desired substance, and the TAT amplification system could possibly be used to produce useful substances as well as deadly ones.
In the life of the AIDS virus, there is commonly a period, after it has infected a cell in the human body, when it hides within the cell's string of genes. It becomes silent, a time bomb waiting to be triggered to multiply rapidly, kill and break out of the cell, infecting many other cells.
The silent virus may be stimulated into action by unrelated infections or other such "challenges" to the cell. The chemical trigger by which the virus awakens and multiplies is TAT.
The Nature report says that this amplification of AIDS takes place chiefly in the portion of the cellular chemistry known as RNA. DNA contains all the raw genetic information of the cell; it is then refined as it is copied into the RNA. From that stage, active molecules are made. They act to create new viruses, or themselves comprise the new viruses.
The discovery is unusual in that it is the only mechanism of its kind known in the type of viruses called retroviruses, and it is one of the most powerful biological amplifiers ever found, Haseltine said.