San Francisco Chronicle - The Voice of the West, 901 Mission Street, San Francisco, CA 94119 - Friday, May 10, 1996, Page A1
David Perlman, Chronicle Science Editor

Their finding comes after a 10- year search for the elusive "co-factors" that scientists have believed must exist for HIV, the virus that causes AIDS, to fuse with the specialized cells it invades to cause disease.

Because of the protein's function, it has been named "fusin." It is probably the first detected of several molecules that enable HIV to invade other immune system cells, as well as cells in the brain and the intestines, scientists said.

And although the research is only beginning -- as the research team leader acknowledged yesterday -- other scientists hailed the discovery as one of the most important since the AIDS virus was first isolated a dozen years ago, and one that could potentially be used to work on new drugs and vaccines for fighting HIV infection.

The finding is being reported today in the journal Science by Edward A. Berger and a team at the National Institutes of Allergy and Infectious Diseases in Bethesda, Md., where much of the government's AIDS research is conducted.

"There has been a long and frustrating search for a co-factor in AIDS, with many ups and downs, but this looks like the real McCoy, and it's a very important finding," said Dr. Warner C. Greene, director of the Gladstone Institute of Virology at the University of California at San Francisco.

Said Dr. Paul Volberding, director of UCSF's AIDS services at San Francisco General Hospital, "It could very well give us another new weapon to prevent the AIDS virus from attaching to cells of the immune system, and it offers great scientific insight into how the AIDS virus works to cause disease."

Since HIV was discovered in 1984, scientists have known that a protein molecule called CD4, which is found on the surface membrane of some immune system cells, acts as the primary receptor for HIV. But they also believed that some other unknown factor was essential for the virus to penetrate the cell, and scientists began seeking it a decade ago.

Recent research has indicated that the mystery factor is a second receptor, and Berger and his laboratory colleagues began their own hunt for it six years ago.

"It took us almost the full six years to figure out what questions we needed to ask and how we might answer them," Berger said in an interview yesterday. "But once we figured out what to do, it took us only three months to get the answer we now call fusin."

To Greene at the Gladstone Institute, the discovery of fusin opens up three vitally important possibilities:

-- It promises to explain for the first time precisely how HIV infects the CD4 cells of the immune system, and how -- if other variants of the fusin molecule are found -- the virus can also invade other white blood cells called macrophages that act as long-term reservoirs for HIV. Still other fusins, in fact, may be involved when HIV invades certain cells in the brain and intestines, Greene said. -- The fusin molecules could also lead the way to an entirely new class of AIDS drugs -- or perhaps even vaccines -- that would be designed to block the fusins and thereby prevent the AIDS virus from invading the cells it now infects. -- Finally, there are strong hopes that scientists will be able to create a true animal model for AIDS.

By genetically engineering rabbits to carry fusins in their bodies, as Berger suggested, it should be possible to infect them with HIV and have them develop AIDS. Until now, scientists searching for an animal model for AIDS have had to content themselves with research on monkeys and simian AIDS, caused by the virus SIV, which is similar to HIV in some respects but is different in important ways. Meanwhile, at least two other laboratories have confirmed Berger's discovery. Berger told The Chronicle yesterday that his own laboratory is also on the hunt for at least one more fusin molecule that probably serves as a crucial "co-receptor" when HIV invades other immune system cells.

"Right now, we're really at the beginning of all this," Berger said, "and because we already know that the fusins are one of a huge family of proteins, they are going to provide a lot of new insights into how HIV causes disease."

At least some of those insights may already be within reach, many scientists now speculate. For example, some people carry the AIDS virus for many years without showing any signs of disease. There are also a small number of people who are known to engage in extremely risky sexual behavior, yet have never tested positive for the AIDS virus.

It may well be that the fusins are either missing or inactive in such people -- and research that solves those mysteries could provide clues for thwarting the HIV virus.

In a statement, leading AIDS researcher Dr. Anthony Fauci, who heads the agency where Berger works, said: "This is a very important study. The findings provide new insights into the mechanisms of HIV's entry into cells, and further elucidate our understanding of the pathogenesis of HIV disease."
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