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Proteins That Could Be Used to Halt HIV Are Identified
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But the researchers also found 237 proteins that had not been known to be necessary for HIV to attack, grow and destroy cells. While not every protein will turn out to be absolutely essential to the virus, most appear to be.
Some proteins are active in steps of HIV's life cycle already targeted by AIDS drugs.
For example, the researchers found a group of proteins involved in letting HIV enter the cell. "Entry inhibitors" are a relatively new class of medications; the first was approved for use in 2003.
The researchers also found proteins involved in helping the virus's long strand of genetic material, called RNA, attach itself to the cellular structure that then copies it. The oldest AIDS drugs, such as AZT, block a stage of this copying process. But the Harvard team found proteins involved in stages not blocked by those drugs but that might theoretically be blocked by future compounds.
The scientists also identified proteins at work in deeper, more mysterious phases of HIV's sojourn in the human cell. Until now, such proteins have been off the pharmaceutical radar screen.
One group is involved in helping the virus get through windows of the cell's nucleus, where the gene-encoding DNA resides. Once HIV gets there, it integrates its genes into the human host's -- ensuring the virus's permanence.
Another group of proteins is involved in studding the outer surface of a newly minted virus with sugar molecules, a process called "glycosylation." Without those sugars, HIV cannot infect a human cell. A drug blocking glycosylation could theoretically make AIDS viruses impotent.
"We found a large number of proteins that were involved in shuttling the virus around the cell," Elledge said. Although they appear necessary for HIV's survival, precisely what they do that the virus needs is unknown.
The new study also shed light on why HIV causes a disease of the immune system.
One-third of the genes identified by Elledge's team are highly active in cells of the immune system -- much more active than in other organs and tissues.
HIV homes in on immune system cells because they offer what it needs.
The study is another example of the potential payoff of the Human Genome Project, the international effort to identify and record the entire human genetic message. This job was largely finished in 2003 and has been refined since then.
The project identified about 21,000 genes and allowed commercial companies to produce "small interfering RNAs," which can selectively block the action of one gene at a time. Scientists are using them to understand, among other things, what genes are involved in disease processes.
Gallo, who is director of the Institute of Human Virology in Baltimore, called the Harvard research "simply an elegant combination of modern molecular biology, new technology and bioinformatics that was used in a manner that has truly led somewhere."
Fauci, whose National Institutes of Health-affiliated laboratory also studies HIV's interaction with cells, said he is impressed by the strategy of selectively inhibiting cellular processes and then watching to see the effects.
"There is nothing that is completely new under the sun, but that is relatively novel," he said.


