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July 25, 2001 Contact: Tim Stephens (831) 459-2495; stephens@cats.ucsc.edu RESEARCHERS UNCOVER HOW A POX VIRUS FOOLS THE IMMUNE SYSTEM For Immediate Release SANTA CRUZ, CA--Research on a rabbit pox virus has shed light on how some viruses sneak past our immune defenses. Scientists at the University of California, Santa Cruz, have found three separate mechanisms by which the pox virus, myxoma, silences the messengers that would normally alert the immune system when a cell is infected. Some of these techniques are also used by herpes viruses and by HIV, the virus that causes AIDS. Most viruses betray themselves to the immune system by their own activities within an infected cell. Viruses cannot replicate on their own, but use the cells they invade as factories to reproduce themselves. Hijacked cellular machinery replicates the virus's genetic material and builds viral proteins. But these viral proteins tip off the host organism's immune system that something is wrong. Specialized molecules in the infected host cells, called major histocompatibility complex (MHC) molecules, carry pieces of the viral proteins to the cell surface, where the immune system's T-cells recognize the proteins as foreign and kill the infected cell. One class of viruses, called DNA viruses, has evolved special genes to block the action of the MHC molecules. "In streamlined viruses, most genes are for virus reproduction," said Martha Zuniga, an associate professor of molecular, cell and developmental biology at UCSC who directed the research. "But in DNA viruses, much of the genome is devoted to evading the host immune system." In the myxoma research, Zuniga and her coworkers found that during the early stages of an infection, the viral DNA produces proteins that pull MHC molecules on the cell surface back inside the cell, where they disintegrate. As the infection progresses, the virus also manages to hold new MHC molecules prisoner within the organelle that makes them. And in the late stages of infection, the virus prevents fragments of its proteins from attaching to transporter molecules that would ordinarily carry protein pieces to the MHC molecules. "It's as if it is covering all its bases for preventing MHC molecules from making it to the cell surface," Zuniga said. She has summarized several years of her research on myxoma in a review article published this month in Recent Research Developments in Virology. Understanding how viruses slip past immune defenses may help researchers learn how to "tweak the system" to control viral infections, Zuniga said. "A treatment is much more likely to work if we know all the tricks a virus has up its sleeve," she said. Myxoma doesn't infect humans, but it shares its evasion techniques with several viruses harmful to humans. HIV also causes MHC molecules on the cell surface to be drawn inside the cell. Adenovirus, a virus that causes respiratory illness, retains MHC molecules in the cellular compartment where they are made. And herpes viruses block pieces of viral protein from being carried to the MHC molecules. But although these viruses produce similar effects, the causes appear to be different. A close examination of myxoma's DNA has revealed that the genes that regulate myxoma's evasion mechanisms are different from those of HIV, adenovirus, and herpes, suggesting that the viruses did not all inherit the same evasion genes from a common ancestor. "They seem to have evolved separately," Zuniga said. Observing myxoma's evasions teaches researchers as much about MHC as about myxoma, Zuniga added. "A lot of what we know about MHC comes from viruses," she said. "You can learn a lot about how something works by seeing how it gets broken." A better understanding of MHC transport might allow scientists to block MHC in the rare situations when its activity is harmful instead of helpful. When a patient receives an organ transplant, for instance, the grafted organ's MHC molecules are among the factors that prompt the body to reject the organ as a foreign object. "If we could selectively manipulate MHC expression, we could turn it on and off at will," Zuniga said. Editor's note: Reporters may contact Zuniga at (831) 459-3180 or zuniga@darwin.ucsc.edu.   ##### Press Release Home | Search Press Releases | Press Release Archive | Services for Journalists
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