Proteins that help HIV grow identified

WASHINGTON — A research team Thursday announced it has identified about 270 proteins the AIDS virus apparently needs to infect a person, instantly providing researchers with dozens of new strategies for blocking or aborting HIV infection.

The vast majority — more than 200 — weren't previously known to play a role in the complicated choreography by which the virus attaches to a cell, enters it, gets copied and establishes permanent residence.

The discovery was made with a technique called a "genomewide scan" that is only a few years old. Current AIDS drugs work by interrupting one of four main steps in HIV's life cycle. The new study suggests there are many more to target.

"This is likely destined to be one of the best papers on HIV for this coming decade," said Robert Gallo, co-discoverer of the AIDS virus, who was not involved in the study. "I think it is terrific."

Anthony Fauci, an AIDS researcher and director of the National Institute of Allergy and Infectious Diseases, said the study "puts on the table many, many more processes that up to this point were unrecognized."

He added quickly: "Now they have their work ahead of them."

The research, led by Stephen Elledge of Harvard Medical School and the Howard Hughes Medical Institute, was published online Thursday by the journal Science.

"We hope this leads to an acceleration of research for cures for AIDS," Elledge said. "It seems like people are starting to forget about AIDS. It is still an incredibly important human-health problem."

The scan is not the last word on what the human immunodeficiency virus, which causes AIDS, needs to infect and destroy human cells, but it's a much more comprehensive inventory than has existed before.

"We'll miss a few things, but the remarkable thing is how much we did find," Elledge said.

Like all viruses, HIV is incapable of growing and doing damage on its own. For that, it must first enter a living cell and hijack some of the molecular and chemical machinery inside.

The virus takes specific enzymes, structures and pieces of membrane the cell uses and turns them to its own purposes. Those include making new copies of itself, bursting out of the cell to infect more cells and, in the case of HIV, not killing some but instead stitching its own genes into them.

Seeking to discover all the proteins HIV employs to complete these tasks, Elledge and his co-workers scanned all 21,000 human genes that encode proteins, blocking them one at a time and seeing what effect that had on the virus' ability to infect a cell. They found 273 proteins the virus seemed to need.

Of that number, 36 had been previously identified. Those proteins included such long-known and well-studied proteins as the CD4 and CCR5 receptors HIV uses to attach to a cell's surface.

But they also found 237 proteins that hadn't been known to be necessary for HIV to attack, grow, and destroy cells. While not every one will turn out to be absolutely essential to the virus, most appear to be.

The scientists also identified proteins at work in deeper, more mysterious phases of HIV's sojourn in the human cell. Until now they 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' 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 that blocked glycosylation could theoretically make AIDS viruses impotent.