New studies by HHMI scientists show how cells use sophisticated signaling mechanisms to control production of interferon.
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Chen explains that each of the three type I interferon-triggering pathways recognizes a particular signal of infection. Invading viruses and bacteria often deliver and replicate their genetic material in the main compartment of the cell known as the cytoplasm, where host DNA is not normally found. A sensor protein called RIG-I detects viral RNA in this cytosolic compartment, which usually indicates the presence of an RNA virus. Cytosolic DNA, which can be introduced by a variety of microbes, including bacteria, DNA viruses, and retroviruses, is detected by a sensor called cGAS, which Chen's lab discovered in 2012. Nucleic acids in membrane-bound compartments called endosomes also indicate viral infection, and are detected by sensors called Toll-like receptors.
Each of these three receptors cooperates with its own adaptor protein to relay its message that an invader is present and interferon is needed. Toll-like receptors work with an adaptor called TRIF, the cGAS receptor works with the adaptor protein STING, and the RIG-I receptor pairs with an adaptor that Chen's lab discovered in 2005 called MAVS.