HIV is certainly a sly pathogen. But now researchers have discovered it is less wily than previously believed. For many years, scientists thought that one reason HIV infections are so successful is that the pathogen avoids immediate immune system detection. Recently, researchers found that HIV does indeed trigger some alarm signals in host cells, but the precise nature of the sensor remained elusive. Now, a team led by Zhijian J. Chen of the University of Texas Southwestern Medical Center has reported that cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase is an HIV sensor (Science 2013, DOI: 10.1126/science/1240933). The team showed that cGAMP synthase detects HIV’s reverse-transcribed DNA, the hallmark of retroviruses. Production of cGAMP in turn triggers signal transduction pathways that activate innate immunity. The authors propose that cGAMP might one day be used in the development of an HIV vaccine as an adjuvant, an ingredient in vaccines used to enhance the response of the immune system to an antigen.