The RNA genome of human immunodeficiency virus type 1 (HIV-1) is enclosed inside a capsid shell that disassembles within a cell in a process known as uncoating. Although HIV-1 uncoating has been linked to reverse transcription of the viral genome in target cells, the mechanism by which uncoating is triggered is unknown. Using time-lapse atomic force microscopy, we analyzed the structure and physical properties of isolated HIV-1 cores during the course of reverse transcription in vitro. We find that, during reverse transcription the pressure inside the capsid increases, reaching a maximum after 7 hours. High-resolution mechanical mapping reveals the formation of a coiled filamentous structure underneath the capsid surface. Subsequently, this coiled structure disappears, the stiffness of the capsid drops precipitously, and the cores are partially or completely ruptured. We propose that the transcription of the relatively flexible ssRNA into the more rigid dsDNA elevates the internal pressure, which triggers uncoating.
