Taking a toll: antiviral drugs activate immune system. (Science News This Week).

Investigators in Japan have now found a major clue to the workings of some of the most promising antiviral medicines under development. These compounds include resiquimod, which scientists are testing against genital herpes.

The new research shows that these drugs, known as imidazoquinolines, appear to activate toll-like receptor 7 (TLR7), a protein on immune cells. Mice genetically engineered to lack TLR7 didn't have the strong, antiviral immune response to imidazoquinolines that normal mice do. When given the drugs, the mutant mice didn't produce the typical inflammatory chemicals, and their immune cells didn't proliferate and mature, Shizuo Akira of Osaka University in Japan and his colleagues report in the February Nature Immunology.

The toll-like receptors are a family of immune-cell surface proteins that detect and respond to microbes (SN: 9/8/01, p. 152). Their involvement in defense against bacteria is well accepted, but it's been less clear whether they help combat viruses. "Our result further reinforces the idea that toll-like receptors are involved in viral recognition," Akira says.

Bruce Beutler of the Scripps Research Institute in La Jolla, Calif., praises the new study but is cautious about its implications for TLR7's natural role. He's unconvinced that TLR7 or other toll-like receptors participate specifically in the body's defense against viruses. The drugs may simply activate a general immune response, he says.

The new paper "does not suggest in any way that TLR7 is a receptor for components of viruses," Beutler concludes.

Akira acknowledges that his team hasn't identified the substance that naturally activates TLR7. It may be a part of a virus or a molecule generated by an animal during a viral infection, he suggests.

Nonetheless, Stephen K. Tyring of the University of Texas Medical Branch in Galveston is thrilled to gain some insight into the workings of resiquimod. "Of all the antiviral drugs I'm working with, it's the most exciting," he says.