Mitochondrial immunity

PROFESSORS PIETRO M. MOTTA © TOMONORI NAGURO / PHOTO RESEARCHERS

The paper:

The finding:

The innate immune system recognizes viral infections inside cells with RIG-I and triggers type I interferon responses with IRF3 and NF-κB. Zhijian Chen's group at the University of Texas Southwestern Medical Center in Dallas discovered a critical missing link in this pathway in mitochondria, a protein they dubbed MAVS.

The surprise:

MAVS is the first mitochondrial protein known to play a direct signaling role in an immune response.

The follow-up:

Subsequent work has shown hepatitis C virus protease NS3/4A can cleave MAVS from the mitochondrion to inactivate the protein and suppress host immunity, notes Ruslan Medzhitov at Yale University in New Haven, Conn.

The work ahead:

"Right now we don't quite understand why MAVS has to be on the mitochondrial membrane for it to signal," Chen says. "We're trying to figure out what other proteins colocalize with MAVS for it to signal." His team also hopes to know how other viruses might target MAVS to evade the host immune system, and how potential MAVS polymorphisms might affect immunity in the human population.