Mitochondrial Protein Mediates Immune Response

A novel mitochondrial membrane protein has been found to play a critical role in the immune system's response to viral infection.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) called the newly identified protein MAVS (mitochondrial antiviral signaling). The protein was found to span the mitochondrial membrane so that it is in contact with both the cell cytoplasm and the mitochondrial genetic material.

Previous studies had shown that viral infection triggered the activation of several transcription factors including NF-kappaB and IRF3. These factors prompt the cell to manufacture interferon, which is a potent antiviral agent. In the current work, published in the August 25, 2005, online edition of Cell, the investigators stopped MAVS production by using RNA interference to silence its gene. Cells in this condition could not activate NF-kappaB and IRF3, and viral replication was stimulated. However, in cells where there was overexpression of MAVS, heightened activity of NF-kappaB and IRF3 enhanced the production of beta-interferon and inhibited viral replication.

"This is the first mitochondrial protein known to be involved in immune defense against any microbial infection,” said senior author Dr. Zhijian Chen, associate professor of molecular biology at the University of Texas Southwestern Medical Center. "Viruses have evolved along with humans and have developed strategies to evade the host's immunity. It is quite possible that some viruses may target MAVS in order to achieve successful infection. In those cases, therapies that enhance MAVS expression or activity may be a viable option for boosting immune responses against viral diseases.”





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U. Texas Southwestern Medical Center