HIV-1 Uncoating Occurs via a Series of Rapid Biomechanical Changes in the Core Related to Individual Stages of Reverse Transcription
Sanela Rankovic, Akshay Deshpande, Shimon Harel, Christopher Aiken, Itay Rousso
Abstract
For successful infection, the HIV-1 genome, which is 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 of HIV-1 uncoating is a pivotal question of long standing. Using atomic force microscopy to analyze individual HIV-1 cores during reverse transcription, we observe a reproducible pattern of stiffness spikes. These spikes were shown to be associated with distinct stages of the reverse transcription reaction. Our findings suggest that these reverse-transcription-induced alterations gradually prepared the core for uncoating at the right time and location in target cells.