Viral inhibition of inflammation: Cowpox virus encodes an inhibitor of the interleukin-1β converting enzyme

Identification of a novel human serpin gene; cloning sequencing and expression of leupin

“…The cleavage site of SCCA is Se~Ser which is unique to this serpin, and the protein has recently been shown to have inhibitory activity against cathepsin L and papain which are cysteine rather than serine proteases [14]. This cross-class inhibitory activity has previously been seen in the viral serpin crmA which inhibits the cysteine protease interleukin-1 fl-converting enzyme (ICE) [15,16].…”

Caspase inhibitors: viral, cellular and chemical

“…1,2 The first caspase inhibitor was cytokine response modifier A (CrmA), a product of cowpox virus that inhibits ICE activity. 3 With the cloning of the CED-3, which is essential for programmed cell death in Caenorhabditis elegans, and recognition of its similarity to ICE, 4 it became clear that caspases were required for cell death in the worm, and therefore that caspase inhibitors might prevent worm cells from killing themselves. Because the mechanisms of programmed cell death in the worm were similar to those for apoptosis of mammalian cells, 5 caspase inhibitors could presumably prevent the death of mammalian cells as well.…”

Alternate functions of viral regulators of cell death

“…Many of these 'nonessential' genes are critical for immune evasion and encode mimics of the TNFR that bind to TNF, such as the cytokine response modifier proteins CrmB, -C, -D and -E of cowpox virus, the M-T2 protein of myxoma virus and S-T2 of Swope fibroma virus. 29,44,45 Alternative strategies to accomplish similar effects were adopted by other viruses that encode vTNF-BP proteins (e.g. the L2 and related proteins encoded by Tanapox virus, Yaba monkey tumor virus, swinepox and Mule deer poxvirus), which share significant amino-acid sequence similarity to MHC class I molecules but lack transmembrane domains.…”