San Francisco Chronicle - Monday June 19, 1989
David Perlman, Chronicle Science Editor

And to add still more bad news about the virus, the scientists also have found evidence that the organism can directly infect a wide variety of cells unrelated to the immune system.

Among them are the skin cells called fibroblasts that line the human bowel and the glial cells that form a supporting network for nerve cells that carry messages throughout the human brain.

The new finding that the power of the AIDS virus to infect cells actually can be increased by "enhancing antibodies" threatens to block the strategies conceived by scientists who are trying to develop vaccines against acquired immune deficiency syndrome, the UCSF researchers say.

It also establishes that the AIDS virus has found new ways to infect human cells by bypassing the most well-known sites on those cells that normally serve as entry points where the virus can attack.

Reports on the disturbing new findings have come from a team headed by UCSF virologist Jay A. Levy, and they have just been published in two major scientific journals: Science and the Proceedings of the National Academy of Sciences. Levy's principal colleagues are Jacques Homsy and Masatoshi Tateno. HIV VIRUS

It has long been known that HIV, the human immune deficiency virus, most frequently infects crucial white blood cells of the immune system called T-helper cells.

Those T-cells carry a protein molecule known as the CD-4 receptor on their surface and a protein on the outer coat of the invading virus binds to that receptor in order to penetrate the cells. Once inside a cell, the AIDS virus can multiply, destroy the target cell and then spread the infection more and more widely.

Now, however, Levy and Homsy have discovered that the AIDS virus can infect cells without binding to the CD-4 receptor at all. Other receptor sites on the surface of other cells apparently also can offer entry points where the virus can invade.

Most antibodies that are mobilized by the immune system serve to neutralize invading organisms. But the UCSF group, examining blood and serum taken from virus-infected guinea pigs, chimpanzees and humans, has found that the virus can effectively stimulate the production of "enhancing" antibodies that enable the virus to infect T-cells without locking on to their CD-4 receptors.

The virus also can infect skin cells like fibroblasts that do not carry CD-4 cells at all, and Levy's group reasons that the enhancing antibodies may provide an alternate infectious pathway that allows the virus to infect other white cells like macrophages through other receptors. GENETIC ENGINEERING

Genetic engineering companies recently developed synthetic soluble CD-4 molecules, and this has led to the hope that CD-4 injected into the bloodstream might act as a decoy to lure invading viruses until they latch on to the artificial molecules and thereby spare T-cells from destruction.

Several medical centers now are conducting trials of genetically engineered CD-4 in volunteer AIDS patients to see whether the decoys can limit continuing infection by the AIDS virus.

But Levy and his colleagues, who have come more and more to realize how complex and unconventional the behavior of the AIDS virus is, warn in their Science paper that "from a therapeutic perspective" the decoy strategy with CD-4 may not be nearly enough to reduce or stop the spread of the AIDS virus.

Other receptor sites on other cells, including those known as Fc receptors also may have to be blocked if the spread of the virus is to be stopped, Levy suggested. BINDING SITE

And somewhere on all the cells that the AIDS virus attacks, scientists may yet find still another binding site common to all of them, Levy suggests. He calls it a "fusion receptor" and believes that it may ultimately prove an essential part of a two-step process for infection by he virus.

In all of the vaccine efforts so far, the goal is to use small protein segments of the outer coat of the virus - or even the entire virus killed by chemicals and radiation - to mobilize antibodies that would neutralize and destroy the invaders.

But Levy is concerned that any attempt to mobilize neutralizing antibodies with potential vaccines may wind up by calling up a host of "enhancing" antibodies that would only make the virus more virulent and increase its ability to kill cells.

Other members of Levy's group in the two reports from his laboratory include Mia Meyer, Sarah Clarkson and Francisco Gonzalez-Scarano.

Always watch for outdated information. This article first appeared in 1989. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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