Immune Defense Against Viruses Depends on Caspase-12

The enzyme caspase-12 has been found to play a critical role in the body's immune defense against pathogenic viruses such as the one that causes West Nile fever.

A report published in the September 5, 2010, online edition of the journal Nature Immunology revealed that the enzyme caspase-12 was critically involved in the mounting of the body's antiviral immune response. Caspase-12 is a cysteine protease belonging to a family of enzymes that cleave their substrates at C-terminal aspartic acid residues. It is closely related to caspase-1 and other members of the caspase family, known as inflammatory caspases, which process and activate inflammatory cytokines such as interleukin-1 and interleukin-18.

To prepare for this study investigators at Yale University (New Haven, CT, USA) and McGill University (Montreal, Canada) genetically engineered a line of mice that lacked the gene to produce caspase-12. This group of mice and a normal control group were then infected with West Nile virus.

Senior author Dr. Erol Fikrig, professor of epidemiology at Yale University, explained, "Mice without caspase-12 protein died more rapidly from West Nile virus infection and had higher levels of virus than normal mice.”

The investigators found that at the molecular level caspase-12 acted by regulating the signaling of RIG-I, an immune system protein involved in the detection of viral infection.

These results open possible avenues of future research on whether the human immune system can be manipulated by pharmacological compounds that would boost the activity of caspase-12 in promoting virus elimination.

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