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Poxvirus Potency Uncovered in New Atomic Map

Scientists at the University of Alabama at Birmingham (UAB) and Saint Louis University used X-ray crystallography to uncover new details about the infectious potency of poxviruses, furthering the understanding of how viral infections can subvert the body’s immune system.

Having high-resolution detail of this protein on hand will speed the discovery of new drugs to combat inflammation and immune diseases such as atherosclerosis and rheumatoid arthritis, the researchers said.

The findings are published in the online edition of the journal Proceedings of the National Academy of Sciences and will soon appear in a print edition.

“Now we have a visual blueprint to guide our future studies on interferon-gamma binding protein, which one day may be used to prevent inflammatory disease,” said Mark R. Walter, Ph.D., an associate professor in the UAB Department of Microbiology and senior author on the study.

Interferon-gamma binding protein (IFN-y) is notorious for the role it plays in helping poxviruses replicate. Normally when a virus enters the bloodstream, the immune system fights back by producing IFN-y, which tells surrounding cells to fight the infection.

Remarkably, somewhere during the evolution of the poxvirus, it captured an IFN-y gene from its host and incorporated some of the protein structure into its own. As a result poxvirus has a very efficient “blocker” of the IFN-y antiviral response, Walter said.

The new study shows this blocking ability through crystallography, the science of mapping the atomic structure of molecules by looking at their interaction with an X-ray beam.

Poxviruses include many classes of the invasive organism, including smallpox, cowpox and monkeypox. Smallpox in particular has played a tragic role in human history: estimates show it caused between 300 million and 500 million deaths in the 20th Century.

Smallpox was declared officially eradicated in 1979, but other poxviruses remain a health threat.

“The damage that the smallpox virus has done to mankind is horrific and enormous, which is why we think it’s so important to understand more about the poxviruses and how they operate,” said Mark Buller, Ph.D., professor of microbiology and immunology at the Saint Louis University School of Medicine and a study author. “The more knowledge we have, the better we should be able to cope with other major viruses and diseases in the future.”

The research was funded by grants from the National Institutes of Health and the American Heart Association.

Troy Goodman | EurekAlert!
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