AIDS `ENTRY' PROTEIN FOUND.

Byline: Warren E. Leary The New York Times

After a decade-long search, scientists Thursday reported finding a protein that is needed to admit the AIDS virus into human immune system cells, beginning a deadly cycle of destruction.

The discovery marks a clear advance in understanding the basic biology of the virus, knowledge that may open up new approaches to research and treatment. Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, described the finding by scientists at his institute as ``a tremendous advance.''

The primary target of the virus is a receptor molecule known as CD-4, which lies embedded in the surface of certain cells. Scientists have long known that CD-4 is insufficient for infection; cells must have some other protein on their surface that the virus, HIV, exploits to effect its entry.

Scientists at the institute in Bethesda, Md., now say they have tracked down the elusive ``co-factor'' protein. They named it ``fusin'' because it helps the coat of the virus to fuse with the cell's outer membrane and inject its genetic material into the cell.

A paper on the discovery by Dr. Edward A. Berger and his colleagues is being published today by the journal Science. The scientists said the finding could lead to genetically engineered mice or rabbits that are susceptible to infection with HIV and could be used to test new drugs and vaccines. In addition, the work may help explain how some people infected with the AIDS virus for years remain healthy and disease resistant, experts said.

``There is no doubt that this is the co-factor for one type of HIV and the thing that so many people have been looking for,'' Fauci said in an interview. ``This is not guesswork, it's the real thing, a very elegant piece of research.''

Dr. James A. Hoxie of the University of Pennsylvania, who also studies how HIV infects cells, called the work ``very exciting stuff that opens doors to several lines of research.'' While the discovery of fusin does not answer all questions about the process the AIDS virus uses to enter and compromise many types of cells, he said, it knocks down a barrier that has stymied some research for years.

``It's a huge advance,'' Hoxie said in an interview. ``This gives us new ways to think about what the virus does in the body.''

Berger and his co-authors, Dr. Yu Feng, Dr. Christopher C. Broder and Paul E. Kennedy, said scientists have known for more than 10 years that the CD-4 receptor on the surface of target cells was a primary attachment point for the virus. However, they said, it quickly became evident that CD-4 was not acting alone in ushering the virus into cells, where the virus can multiply.

``CD-4 grabs HIV and attaches it firmly to the cell surface, but it doesn't allow the virus to fuse to the cell membrane and penetrate,'' Berger said in an interview. ``Our research shows that a second molecule, fusin, is required for certain strains of HIV to fuse with and enter into cells. And this makes us believe there may be other fusion co-factors that serve the same purpose for other HIV strains.''

Berger's research focused on HIV-1, the most common strain of the virus. A related virus, HIV-2, found mostly in western Africa, may have a slightly different co-factor but one that is probably in the same family of proteins, Berger said.

The researchers developed a sensitive assay to test the many proteins found on blood cells to isolate the one that worked with CD-4 to aid viral fusion. They altered a vaccinia virus to carry a gene into mouse cells that caused them to turn blue when exposed to a special stain when an HIV surface protein fused with CD-4 target cells.

The mouse cells, altered to produce human CD-4, then were exposed to a battery of genetic materials that made proteins that were candidates for helping HIV fuse to CD4. Through a process of elimination that involved repeatedly dividing cell cultures to find the most blue cells, the researchers narrowed their search to one protein, fusin.

``We started with a haystack, divided it into 100 portions and tested each one to see if there was activity,'' Berger said. ``We then took the one that had the most activity, and divided it into 100 parts and tested them. Eventually, we got to the piece of hay with the activity we were looking for.''

Berger said fusin helps HIV-1 infect white blood cells of the immune system called T-cells. T-cells are a major target of HIV after the viral infection begins causing symptoms of AIDS and the immune system is compromised.

Earlier in an HIV infection, before there are symptoms of disease, the virus attacks another group of immune system cells called macrophages. Berger said another co-factor, perhaps a relative of fusin, is responsible for helping HIV penetrate the macrophages. He said identifying that co-factor would be a major goal of future research.

Other new research stemming from the fusin work may lead to new animal models for studying HIV infections, scientists said. Work on new vaccines or drugs against HIV has been limited because few animals, other than expensive and increasingly rare primates, can be infected with the virus.

Through genetic engineering, researchers have developed mice and rabbits that have human CD-4 receptors on their cells, researchers said, but HIV does not infect and reproduce very well in these cells. Berger said it may be possible to produce animals that have both human CD-4 and fusin on their cells, which may make the animals susceptible to HIV infection and better models for testing potential treatments.