Getting a close look at a virus-detecting RIG

Viruses ranging from common influenza to hepatitis C rely on strands of RNA to infect human cells and spread their genetic information. Yale researchers have now made a step toward understanding how the human immune system recognizes viral RNA strands to mount an immune response, work that could reveal new ways to target such viruses with drugs.

Scientists knew that a protein called RIG-I binds to viral RNA that’s entered a human cell and alerts the cell of its presence. To find out more about how RIG-I recognizes viral infection, Anna Marie Pyle, Ph.D., the William Edward Gilbert Professor of Molecular, Cellular, and Developmental Biology, along with postdoc Dahai Luo, Ph.D., and Brett Lindenbach, Ph.D., assistant professor of microbial pathogenesis, determined the 3-D structure of RIG-I bound to double-stranded RNA (dsRNA), which is produced when viruses replicate.

As reported in the October 14, 2011 issue of Cell, the group discovered that when bound to dsRNA, RIG-I undergoes a dramatic change in shape, in which one section of the protein folds out to make room for the RNA. The authors write that their work on RIG-I’s structure “reveals multiple strategies for therapeutic design.”