Invited
Unraveling the mechanism of HIV genome release from the capsid using mechanical and morphological analysis

For successful infection, the human immunodeficiency virus type 1 (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. The mechanism that triggers uncoating is a pivotal question of long standing. By using atomic force microscopy, we analyzed the mechanical properties and morphology of isolated WT and hyperstable mutants of HIV capsids durring reverse transcription. We found that during reverse transcription the pressure inside the capsid increases until the internal stress exceeds the strength of the capsid structure and the capsid breaks open. The application of AFM technologies to study purified HIV-1 cores represents a new experimental platform for elucidating additional aspects of capsid structure, disassembly and HIV-1 uncoating.