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New protein vital for immune response is found in surprise location

DALLAS Aug. 25, 2005 A newly discovered protein not only is vital to the immune system's ability to fight off viral infections but also has been found in an unexpected location within the cell, causing researchers to rethink previous notions about the workings of the human immune system.

Researchers at UT Southwestern Medical Center said their findings may lead to new therapies aimed at preventing and treating viral diseases such as the flu, hepatitis, West Nile virus and SARS. The study is available online and will appear in the Sept. 9 issue of the journal Cell.

Working with cultured cells, researchers found that the protein, made by a gene they discovered and named MAVS, is located in an unexpected place within the cell in the membrane of an organelle called the mitochondrion, which until now was best known for generating energy required for daily life.

"This is the first mitochondrial protein known to be involved in immune defense against any microbial infection," said Dr. Zhijian "James" Chen, associate professor of molecular biology at UT Southwestern and the study's senior author. "This discovery puts mitochondria on the map in terms of immunity, and it opens up a new avenue of research in immunology."

The researchers modified normal cells so that the cells could not produce the MAVS protein, which is short for Mitochondrial Anti-Viral Signaling protein. Without MAVS, the cells were highly vulnerable to infection with two common viruses in a class called RNA viruses Other RNA viruses include hepatitis C, West Nile, SARS and the flu viruses.

Cells altered to produce an overabundance of MAVS were protected from dying from viral infection.

"These results raise the possibility that variations in the expression levels of MAVS may endow different individuals with varying ability to fight off viral diseases," said Dr. Chen, who also is an investigator with the Howard Hughes Medical Institute. "Viruses have evolved along with humans
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Contact: Amanda Siegfried
amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
25-Aug-2005


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