Once the viral DNA has been created, it moves into the cell nucleus and inserts itself into the cell's genes, helped by the enzyme integrase (defined).
Once this process is completed, the cell is programmed to reproduce hundreds or thousands of copies of viral RNA. And every one of the cell's daughters will be likewise programmed for that wretched task.
Big problems arise from HIV's ability to insert its genes into the cell's genetic material. Most other viruses stay in the cell's cytoplasm (defined), where they are more accessible to the immune system. "That's the major difficulty -- this fact of integration," says AIDS researcher Robert Gallo, since it means medical science must do something that has "never been done in virology -- preventing the initial infection."
Polio vaccines, Gallo notes, don't have to prevent the initial infection. Instead, they make the body hostile to the polio virus by creating immune cells programmed to recognize and kill the virus. This prevents a damaging number of polio viruses from reaching the nerve cells they typically target.
But once HIV's genes are spliced into the host cell's chromosomes, they can't be killed without killing the entire cell.
This critical step of insertion into the host DNA has become the target of at least one new drug, Zintevir, or AR-177. Like the first AIDS drugs, it's intended to inhibit the action of an enzyme, but in this case, the enzyme is integrase. The integrase inhibitor is now in preliminary clinical trials. According to its maker, Aronex pharmaceuticals, "Aronex believes that ZintevirTM is the most potent integrase inhibitor that has been described to date and is the first integrase inhibitor that has entered a human clinical trial." We expected them to be optimistic, but we also hope it works.
The new viral RNA is almost ready for its dirty work. But before it exits the cell, the proteins surrounding it must be chopped to length.
