Number of HIV targets grows
Researchers say they have found more proteins vulnerable to attack by the virus.
WASHINGTON - The AIDS virus has to hijack human proteins to do its damage, but scientists until now have known only a few dozen of its targets. Yesterday, Harvard researchers unveiled a surprisingly longer list, an important first step in the hunt for new drugs.
HIV is, on its face, a simple virus, consisting of just nine genes. Yet it makes up for that bare-bones structure in a sinister and complex way - by literally taking over the cellular machinery of its victims so it can multiply and then destroy.
"It's as if a small terrorist group attacks a town with a tank, and then converts the town into a tank factory," said Stephen Elledge, a Harvard Medical School geneticist who helped to write the study.
"They would have to take over the existing infrastructure to get these things replicated," he said.
The proteins it exploits have been dubbed HIV dependency factors, and 36 had been discovered. The new research, published online yesterday by the journal Science, found 273 of these potential HIV targets.
Led by Elledge, the team used a technique called RNA interference that can disrupt a gene's ability to do its job and make a protein. One by one, they disrupted thousands of human genes in test tubes, dropped in some HIV, and watched what happened. If HIV couldn't grow well, it signaled the protein that the gene that had failed to produce must be the reason.
Drugs that stop cells from cooperating with the lethal virus might be valuable alternatives to those that attack the ever-changing virus directly, said David Baltimore, a California Institute of Technology biologist and HIV researcher.
"This provides a very important class of leads for the synthesis of new drugs that can prevent HIV growth," said Baltimore, who was not involved in the study.
"The nice thing is that these cellular targets mutate at a much slower rate than viral targets, so resistance is less likely to arise."
While some of these genes and proteins may be too important to cell survival to be blocked or altered, others may be targets. It will take far more research to figure out the role each of these proteins plays in HIV's life cycle.
Most of today's AIDS drugs work by targeting the virus itself. In August, the government approved sale of the first drug that works by blocking an HIV dependency factor, a cellular doorway called CCR5. The hope is that this longer list of those factors will point toward spots where similar drugs might work.