How Lassa virus breaks and enters Lassa virus, which spreads from rodents to humans, infecting about half a million people every year, can lead to deadly hemorrhagic fever. Like many viruses, Lassa virus binds to cell surface receptors. Jae et al. now show that to enter a cell, the virus requires a second receptor, this one inside the infected cell. This requirement sheds light on the “enigmatic resistance” of bird cells to Lassa virus observed three decades ago. Although bird cells have the cell surface receptor, the intracellular receptor cannot bind the virus, stopping it in its tracks. Science , this issue p. 1506