The virus that causes a common form of AIDS-related cancer sabotages the body's immune system in a novel and previously unsuspected way, University of California, San Francisco scientists have discovered.

When the virus associated with Kaposi's sarcoma (KS) invades a cell, two of the KS virus genes direct the cell to remove sentries posted on the cell surface and ship them to the interior for destruction, the researchers report. The sentries -- proteins of the major histocompatibility complex, or MHC-1 -- constitute one of the cell's major lines of defense, and would otherwise tag the invaders for quick attack by the host immune system.

Other viruses sometimes disarm this line of defense too, but typically by blocking deployment of the sentries rather than getting the cell to recall them and target them for internal destruction. The approach evolved by the Kaposi's- associated herpesvirus (KSHV) is a novel strategy in the arms race between viruses and the immune system, says Donald Ganem, MD, an Investigator of the Howard Hughes Medical Institute and professor of microbiology and immunology at UCSF. Ganem is senior author on a study describing the new research.

In the virus-immune system arms race, each new deployment by one side is met with a riposte from the other, Ganem says. "And there's every reason to believe this race isn't over. With every new strategy for host defense comes a selective pressure for the virus to find a way to circumvent that defense."

The research describing the KS virus genes and their function in immune sabotage is published in the current issue of the Proceedings of the National Academy of Sciences. First author is Laurent Coscoy, PhD , an HHMI post-doctoral researcher in Ganem's lab.

One of the intriguing findings in the new research is the discovery that the two proteins responsible for sequestering the MHC sentries
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
19-Jun-2000