The mechanical properties of HIV-1 capsid during reverse transcription: insights into uncoating

For successful infection, the HIV-1 genome, which is in the
form of a single-stranded RNA enclosed inside a capsid shell,
must be reverse transcribed into double-stranded DNA and
released from the capsid (in a process known as uncoating)
before it can be integrated into the target cell genome. Although HIV-1 uncoating has been linked to reverse transcription of the viral genome in target cells, the mechanism
by which uncoating is initiated 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 to a value below that of a pre-reverse transcription
core, and the cores partially or completely rupture. We propose that the transcription of the relatively flexible ssRNA
into the more rigid RNA-DNA hybrid elevates the pressure
within the core, which induces uncoating.