Viral interference with IL-1 and Toll signaling

The cytoplasmic domain of both the IL-1 receptor (IL1R) and of molecules that function in host defense called Toll-like receptors (TLR) are homologous to one another and thus are called TIR (Toll/IL-1 receptor) domains (1). Two publications in recent issues of PNAS have sought for more Toll-like receptors in two different organisms. One paper, by Bowie et al. (2), describes the discovery of TLRs in the vaccinia virus, suggesting that the virulence of pox viruses depends on this measure to counter host defense. This is quite typical of pox viruses, which have over the years acquired several cytokine and cytokine-receptor genes that participate in modulating the antiviral host response. Another paper, by Tauszig et al. (3), describes more Toll-like genes in the fruit fly Drosophila melanogaster, where these genes were first described. Initially, Toll was known to be involved in dorso-ventral axis formation in the fly embryo. However, it was discovered several years ago by the Jules Hoffmann group in Strasbourg, France, that these genes also participate in a fundamental form of host defense, which was until that time unknown (4). It is now clear, from several publications over the last 5 years, that the activation of the TIR domain leads to activation of NF-κB, which in turn activates a variety of cytokines, chemokines, and costimulatory molecules that are mounted on the cell surface. Furthermore, it is clear that the TIR domain is central to the functioning of an ancient form of host defense, without which the adaptive …