First discovery of an immune system counter attack in the virus wars

In their endless war against the immune system, viruses rapidly evolve new evasive strategies. But scientists have uncovered the first genetic evidence of counter attack by the beleaguered immune defenses: Immune proteins that viruses once exploited have apparently evolved the ability to call in attacks against their former exploiters.

This case of immune proteins turning the table on the invaders may be quite common the researchers think, since genetic evolution appears to race fastest where the fighting is fiercest in the give-and take battle between pathogens and the receptors that encounter them on the surface of immune cells.

The research led by UCSF scientists will be published online April 11 by SCIENCE (http://www.sciencexpress.org) and will appear in the journal several weeks later.

The discovery comes from a study of a strain of mice able to resist infection by a virus known as murine cytomegalovirus, or MCMV, related to the human cytomegalovirus, smallpox virus, Epstein-Barr and other human viruses.

The key finding involves changes that have apparently occurred in an inhibitory receptor a protein on the surface of natural killer, or NK, immune cells that normally prevents killer cells from launching an autoimmune attack against ones own tissues. The inhibitory receptor sends a stop signal when it recognizes and binds to self molecules on normal, healthy tissue, and the signal reigns in the killer cells. Other researchers have found evidence that viruses have evolved the ability to make decoys of these self molecules, thereby triggering the stop signal and protecting themselves from immune attack.

The new research shows that in some strains of mice resistant to MCMV, the immune system has adapted by retaining the ability to bind to the virus signal but losing the ability to bind to self molecules. As a result, the former inhibitory receptor has become an activating re

Contact: Wallace Ravven
University of California - San Francisco

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